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Cited by 87T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

Comparing Mouse and Human Tissue-Resident γδ T Cells

Open access
Qu, Guanyu, Wang, Shengli, Zhou, Zhenlong, Jiang, Dawei, Liao, Aihua, Luo, Jing·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2022.891687PMC PMC9215113
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Abstract

Circulating immune cell compartments have been extensively studied for decades, but limited access to peripheral tissue and cell yield have hampered our understanding of tissue-based immunity, especially in γδ T cells. γδ T cells are a unique subset of T cells that are rare in secondary lymphoid organs, but enriched in many peripheral tissues including the skin, uterus, and other epithelial tissues. In addition to immune surveillance activities, recent reports have revealed exciting new roles for γδ T cells in homeostatic tissue physiology in mice and humans. It is therefore important to investigate to what extent the developmental rules described using mouse models transfer to human γδ T cells. Besides, it will be necessary to understand the differences in the development and biogenesis of human and mouse γδ T cells; to understand how γδ T cells are maintained in physiological and pathological circumstances within different tissues, as well as characterize the progenitors of different tissue-resident γδ T cells. Here, we summarize current knowledge of the γδ T phenotype in various tissues in mice and humans, describing the similarities and differences of tissue-resident γδ T cells in mice and humans.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review compares tissue-resident γδ T cell subsets in mice and humans across skin, lung, and uterus, arguing that functional potential tracks Vγ usage in mice but Vδ usage in humans. It concludes that tissue-specific γδ T cell biology is shaped by both organ and species, and that human tissue γδ T cells remain comparatively under-characterized.

Key findings

  • γδ T cells are a minor fraction (1–5%) of circulating T cells in blood and secondary lymphoid organs but reach 10–100% of T cells in epithelial tissues such as the reproductive tract, skin epidermis, and gastrointestinal tract.
  • Mouse γδ T cell development proceeds in layered ontogenic waves: Vγ5Vδ1 DETC precursors appear as early as embryonic day 15 and seed the epidermis; Vγ6Vδ1 cells follow into tongue, dermis, uterus, testis, abdominal cavity, adipose tissue, and meninges; perinatal Vγ7+ cells enter the intestine; polyclonal Vγ1+/Vγ4+ populations distribute more systemically.
  • In humans, Vγ9Vδ2+ chains rearrange as early as weeks 5–6 of gestation in fetal liver and after 8 weeks in fetal thymus, dominating the repertoire by mid-gestation (20–30 weeks); Vδ1+ cells are the major γδ population in intestine and skin, and Vδ3+ cells are enriched in liver and gut.
  • Species differences are organ-specific: human skin lacks a direct DETC equivalent and its γδ cells rarely secrete IL-17, whereas mouse dermal Vγ4+/Vγ6+ cells are the main IL-17 producers in psoriasis/dermatitis models; in lung cancer, higher intratumoral Vδ1 γδ T cells is reported as a poor prognosis factor.

Methods

  • Narrative literature review; no primary data, no systematic search strategy or meta-analysis is described.
  • Synthesizes published mouse and human studies on γδ T cell development, thymic selection, and tissue residency, organized by organ (skin, lungs, uterus) with a summary table of subsets, distributions, cytokines, and markers.
  • Figures 1 and 2 and Table 1 compile developmental waves, tissue-homing schematics, and subset markers (e.g., CD27, CD45RB, CD44, CCR6, NKG2D).

Limitations

  • Stated by the paper: the origin of human tissue-resident γδ T cells is "technically challenging to address"; the functions of human epidermal γδ T cells "are just beginning to be elucidated"; lack of in vitro methods to expand Vδ1 γδ T cells in lung cancer has prevented clarifying their role; and it is difficult to determine whether circulating Vδ1+ cells in pregnancy are simply spillover from the fetal–maternal interface.
  • Evident from the text: as an unsystematic narrative review, it provides no search criteria, inclusion rules, or quantitative synthesis, and several comparative claims (e.g., human γδ cells "rarely secrete IL-17") are asserted without supporting data presented in the text.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fimmu.2022.891687

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

27 of 49 cited sources checked · 10 supported · 2 flagged · accuracy not yet measured

  • Premisecitation

    Certain subsets of γδ T cells are present in much higher proportions (10-100%) in epithelial tissues, such as the reproductive tract, skin epidermis, and gastrointestinal tract.

    “However, certain subsets of γδ T cells are present in much higher proportions (10–100%) in epithelial tissues, such as the reproductive tract, skin epidermis, and gastrointestinal tract (2).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] Nielsen, 2017, Gamma Delta T Cells in Homeostasis and Host Defence of Epithelial Barrier Tissues, Nat Rev Immunol source
  • Premisecitation

    The γδ T pool residing in a given tissue is the result of the wave of development from fetal to adult life, referred to as layered ontogeny.

    “From further mouse studies, it is nonetheless becoming increasingly clearer that the γδ T pool residing in a given tissue is the result of the wave of development from fetal to adult life, referred to as layered ontogeny (8).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [8] Vantourout, 2013, Six-Of-the-Best: Unique Contributions of γδ T Cells to Immunology, Nat Rev Immunol source

      In “Selective homing and retention” (page unavailable), the paper describes successive developmental waves homing to different mouse tissues, but says this explains tissue-localised compartments only “in part”; retention also matters. In “γδ T cells and ontogeny” (page unavailable), it says fetal-origin cells may persist into adulthood and combine with cells from postnatal progenitors. The claim overstates this qualified account as a settled explanation for the pool in any given tissue. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    There is no direct equivalent of DETCs in human skin as the immune cell composition of the epidermis is subject to species-specific differences.

    “There is no direct equivalent of DETCs in human skin as the immune cell composition of the epidermis is subject to species-specific differences (2).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] Nielsen, 2017, Gamma Delta T Cells in Homeostasis and Host Defence of Epithelial Barrier Tissues, Nat Rev Immunol source
  • Premisecitation

    In wild-type mice, the epidermal T cell compartment is dominated by a highly specialized γδ T cell subset termed dendritic epidermal T cells (DETCs).

    “In wild-type mice, the epidermal T cell compartment is dominated by a highly specialized γδ T cell subset termed dendritic epidermal T cells (DETCs) (29).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Xu, 2021, Epidermal Resident γδ T Cell Development and Function in Skin, Cell Mol Life Sci source

      The Abstract identifies DETCs as a unique γδ T-cell population enriched in the mouse epidermis, and the Introduction describes their specialized receptor and residence there. Neither passage establishes that DETCs dominate the epidermal T-cell compartment in wild-type mice. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Butyrophilins (BTN3A1 and BTN3A2/3) are important for Vγ9Vδ2+ T cell recognition.

    “Third, consistent with related immunobiology, butyrophilins (BTN3A1 and BTN3A2/3) are important for Vγ9Vδ2+ T cell recognition (22).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Vantourout, 2018, Heteromeric Interactions Regulate Butyrophilin (BTN) and BTN-Like Molecules Governing γδ T Cell Biology, Proc Natl Acad Sci USA source
  • May combine two claims. 40
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Premisecitation

    Mouse γδ T cell subsets are distinguished by different TCR Vγ chains, whereas human γδ T cell subsets are often distinguished by Vγ chain usage.

    “The mouse γδ T cell subsets are distinguished by different T cell receptor(TCR) Vγ chains, whereas human γδ T cell subsets are often distinguished by Vγ chain usage (2).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] Nielsen, 2017, Gamma Delta T Cells in Homeostasis and Host Defence of Epithelial Barrier Tissues, Nat Rev Immunol source

      The section “γδ T cells in the epithelial layer of skin and intestine” supports the mouse half of the claim but says human subsets are often distinguished by Vδ usage, not Vγ usage. No page number is provided in our copy. (LLM, conf=0.92)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    γδ T cells that develop without pre-programming in the thymus and receive the TCR signal in the periphery develop as adaptive types, whereas γδ T subsets that receive the signal in the thymus are innate types, and those which receive the TCR signal in the periphery but during an early phase of life get converted into innate-like γδ T cells.

    “γδ T cells that develop without pre-programming in the thymus and receive the TCR signal in the periphery develop as adaptive types, whereas γδ T subsets that receive the signal in the thymus are innate types, and those which receive the TCR signal in the periphery but during an early phase of life get converted into innate-like γδ T cells (12).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Parker, 2020, Regulation of γδ T Cell Effector Diversification in the Thymus, Front Immunol source

      Split into 3 atoms — 0 confirmed, 2 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    γδ T cells are a small subset of CD3-positive T cells in peripheral blood but occur at increased frequency in mucosal tissues in mice and humans.

    “Gamma delta (γδ) T cells are a small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues in mice and humans (1).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Kabelitz, 2020, Gamma Delta T Cells (Gamma Delta T Cells) in Health and Disease: In Memory of Professor Wendy Havran, Cells source

  • May combine two claims.

    Premisecitation

    Although DETCs are thymically programmed to produce IFN-γ rather than IL-17 in wild-type mice, DETCs on a skint-1-deficient background are primarily committed toward an IL-17 effector phenotype.

    “Although DETCs are thymically programmed to produce IFN-γ rather than IL-17 in wild-type mice, DETCs on a skint-1-deficient background are primarily committed toward an IL-17 effector phenotype (35, 36).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [35] MacLeod, 2013, Dendritic Epidermal T Cells Regulate Skin Antimicrobial Barrier Function, J Clin Invest source

      The Discussion (page unavailable) says Skint1 engagement in fetal thymic DETC precursors induces signals associated with IFN-γ expression, supporting the wild-type precursor portion of the claim. It also says mature DETC cytokine fates do not appear to be preprogrammed by that event. Our copy does not report that DETCs on a Skint1-deficient background are primarily committed to IL-17. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [36] MacLeod, 2014, Skin-Resident T Cells Sense Ultraviolet Radiation-Induced Injury and Contribute to DNA Repair, J Immunol source

  • May combine two claims.

    Premisecitation

    When assembling TCRs, human γδ T cells express seven bona fide Vγ genes but only three Vδ genes.

    “When assembling TCRs, human γδ T cells express seven bona fide Vγ genes but only three Vδ genes (27).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Adams, 2011, D, and J Gene Segments Used in the Primate γδ T-Cell Receptor Reveals a Dichotomy of Conservation and Diversity, Proc Natl Acad Sci U.S.A. source

  • May combine two claims.

    Premisecitation

    IL-17 release by DETCs can promote DNA repair following exposure to UV radiation and protect the skin against potential opportunistic infections by releasing keratinocyte-derived antimicrobial peptides.

    “IL-17 release by DETCs can promote DNA repair following exposure to UV radiation and protect the skin against potential opportunistic infections by releasing keratinocyte-derived antimicrobial peptides (37, 38).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [37] Holtmeier, 2001, The TCR Delta Repertoire in Normal Human Skin is Restricted and Distinct From the TCR Delta Repertoire in the Peripheral Blood, J Invest Dermatol source
    • cites [38] Daniels, 2020, Cellular Origins and Genetic Landscape of Cutaneous Gamma Delta T Cell Lymphomas, Nat Commun source

      The Discussion (page not provided) says that, in mouse models, γδ T cells protect against microbes and contribute to epidermal homeostasis. It does not say that DETC-derived IL-17 promotes DNA repair after UV exposure or that keratinocyte-derived antimicrobial peptides provide the claimed protection. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    SKINT1, a mouse-specific member of the butyrophilins (BTNs) family that is exclusively expressed in the thymic epithelium and the epidermis, was shown to be essential for thymic selection and skin-specific homing of Vγ5Vγ1 T cell.

    “SKINT1, a mouse-specific member of the butyrophilins (BTNs) family that is exclusively expressed in the thymic epithelium and the epidermis, was shown to be essential for thymic selection and skin-specific homing of Vγ5Vγ1 T cell (32).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [32] Sutoh, 2018, Origin and Evolution of Dendritic Epidermal T Cells, Front Immunol source

      The “SKINT1 and the SKINT Gene Family” section supports SKINT1’s expression in thymic epithelial cells and skin keratinocytes, and its role in thymic selection and production of cells migrating to the epidermis. But the paper identifies those cells as Vγ5Vδ1, not Vγ5Vγ1, and attributes impaired epidermal migration to defective thymic selection rather than establishing a separate skin-specific homing function. The “Evolution of the SKINT Gene Family” section also says authentic Skint1 genes occur in murids, not only mice. No page numbers are provided for these passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    IL-12 and IL-18 promote IFN-γ production, while IL-1β and IL-23 drive γδ T cells towards IL-17-producing cells.

    “IL-12 and IL-18 promote IFN-γ production, while IL-1β and IL-23 drive them towards IL-17-producing cells (14).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Ribeiro, 2015, Five Layers of Receptor Signaling in γδ T-Cell Differentiation and Activation, Front Immunol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    αβ T cells and γδ T cells arise from a common progenitor known as a double-negative cell (DN; lacking CD4 and CD8 expression) in the thymus.

    “αβ T cells and γδ T cells arise from a common progenitor known as a double-negative cell (DN; lacking CD4 and CD8 expression) in the thymus (11).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Koch, 2008, Delta-Like 4 Is the Essential, Nonredundant Ligand for Notch1 During Thymic T Cell Lineage Commitment, J Exp Med source

      The introductory passage (page not provided) identifies the earliest thymic progenitors as double-negative thymocytes because they lack CD4 and CD8. It does not state that αβ and γδ T cells both arise from a common DN progenitor; the Methods mention TCRγδ only as a staining marker. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Vγ9 and Vδ2 variable gene segments are the first γ/δ chains to undergo rearrangement in development, detected in the fetal liver from as early as weeks 5~6 of gestation and in the fetal thymus after 8 weeks of gestation.

    “The Vγ9 and Vδ2 variable (V) gene segments are the first γ/δ chains to undergo rearrangement in development, detected in the fetal liver from as early as at weeks 5~6 of gestation (15) and in the fetal thymus after 8 weeks of gestation (16).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [15] McVay, 1996, Extrathymic Origin of Human Gamma Delta T Cells During Fetal Development, J Immunol source

      The supplied copy’s Materials and Methods and Results and Discussion passages (pp. 1585–1586) concern NK-cell receptors and HLA-B*2705, despite the stated source title. Searches for Vγ9/Vδ2 rearrangement and fetal-liver development at 5–6 weeks returned no relevant passage. The claim attributed to citation (15) cannot be verified from this copy; the thymus timing is attached to citation (16). (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [16] McVay, 1998, The Generation of Human Gammadelta T Cell Repertoires During Fetal Development, J Immunol source

  • May combine two claims.

    Premisecitation

    In humans, the subset of γδ T cells localized in human skin is Vδ1+ γδ T cells, which express oligoclonal clonal sequences distinct from circulating γδ T cells.

    “In humans, the subset of γδ T cells localized in human skin is Vδ1+ γδ T cells, which express oligoclonal clonal sequences distinct from circulating γδ T cells (39).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [39] Nakasone, 2007, Accumulation of Gamma/Delta T Cells in the Lungs and Their Roles in Neutrophil-Mediated Host Defense Against Pneumococcal Infection, Microbes Infect source

      The Introduction and Discussion address γδ T-cell subsets in mouse infection and pulmonary inflammation, not human skin. Searches for human skin Vδ1+ cells, oligoclonal sequences, and differences from circulating γδ T cells found no passage addressing the claim. The cited paper’s copy therefore cannot verify it. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Vδ2 is the largest subset of circulating human γδ T cells in the blood, which gets rapidly recruited to the mucosal surface to participate in the clearance of localized infection.

    “Vδ2 is the largest subset of circulating human γδ T cells in the blood, which gets rapidly recruited to the mucosal surface to participate in the clearance of localized infection (17).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [17] McCarthy, 2018, Human γδ T-Cell Control of Mucosal Immunity and Inflammation, Front Immunol source

      The section “γδ T-Cells Stimulate Complex Mucosal Leukocyte Responses” (page unavailable) says Vδ2+ cells are rapidly recruited to mucosal tissues in higher primates and mediate protection against bacteria in humanized mice. It does not establish that Vδ2+ cells are the largest subset of circulating human γδ T cells, and the recruitment and protection findings come from different models. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The growth of dermal γδ T cells preferentially requires IL-7, whereas IL-15 is mandatory for the generation of γδ TCR-expressing intra-epithelial lymphocytes (IELs).

    “The growth of dermal γδ T cells preferentially requires IL-7, whereas IL-15 is mandatory for the generation of γδ TCR-expressing intra-epithelial lymphocytes (IELs) (13).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Dunne, 2020, Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder, Front Immunol source

      The section “A Role for Conventional and Unconventional Lymphocytes?” discusses γδ IELs and links IL-15 to activation and expansion of cytolytic CD8 IELs, but it does not state that IL-15 is mandatory for generating γδ TCR-expressing IELs. Searches for dermal γδ T-cell growth and IL-7 also found no passage addressing the claimed requirement. (LLM, conf=0.70)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Current views in the field suggest that the functional potential of mouse γδ T cells is related to the use of Vγ, while the functional potential of humans is related to the use of Vδ.

    “Current views in the field suggest that the functional potential of mouse γδ T cells is related to the use of Vγ, while the functional potential of humans is related to the use of Vδ (26).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [26] Prinz, 2013, Functional Development of γδ T Cells, Eur J Immunol source

  • May combine two claims.

    Premisecitation

    In healthy pregnant women, there was an accumulation of Vδ1+ circulating cells, in contrast to women with recurrent abortions where the Vδ2+ circulating cells dominated.

    “In healthy pregnant women, there was an accumulation of Vδ1+ circulating cells, in contrast to women with recurrent abortions where the Vδ2+ circulating cells dominated (47).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [47] Mincheva-Nilsson, 2003, Pregnancy and Gamma/Delta T Cells: Taking on the Hard Questions, Reprod Biol Endocrinol source

  • May combine two claims.

    Premisecitation

    Vγ9Vδ2 γδ T cells specifically recognize the phosphoantigen HMB-PP, which is abundantly produced by Mycobacterium tuberculosis, and this selective immunity elicits rapid and long-lasting memory, rapidly producing more IL-17 and IFN-γ upon pathogen-specific re-challenge, enhancing bacterial clearance.

    “Vγ9Vδ2 γδ T cells specifically recognize the phosphoantigen (E)-4-hydroxy-3-methylbutylpyrophosphate (HMB-PP), which is abundantly produced by Mycobacterium tuberculosis, and this selective immunity elicits rapid and long-lasting memory, rapidly producing more IL-17 and IFN-γ upon pathogen-specific re-challenge, enhancing bacterial clearance (44).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [44] Bao, 2017, Characterization of γδ T Cells in Patients With non-Small Cell Lung Cancer, Oncol Lett source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Mouse Vγ6/Vδ1 cells are closely associated with the epithelial tissue of the female reproductive tract and account for a major proportion of γδ T cells in uterine tissue.

    “Mouse Vγ6/Vδ1 cells are closely associated with the epithelial tissue of the female reproductive tract and account for a major proportion of γδ T cells in uterine tissue (47).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [47] Mincheva-Nilsson, 2003, Pregnancy and Gamma/Delta T Cells: Taking on the Hard Questions, Reprod Biol Endocrinol source

      In “γδT cells at the feto-maternal interface” (page unavailable), the paper says Vδ1 is preferentially used by γδ T cells in normal and pregnant mouse uteri. The “Vδ usage” section (page unavailable) places resident γδ T cells at uterine and vaginal epithelial surfaces. The copy does not identify those cells as Vγ6/Vδ1 or establish that this specific subset accounts for a major proportion of uterine γδ T cells. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    When lung infection occurs, Vγ1+, Vγ4+, and Vγ6+ T cells proliferate in the lung, and Vγ4+ γδ T cells secrete CXC chemokine ligand 2 (CXCL2; also known as MIP2) and TNF to promote neutrophil recruitment.

    “When lung infection occurs, Vγ1+, Vγ4+, and Vγ6+ T cells proliferate in the lung, and Vγ4+ γδ T cells secrete CXC chemokine ligand 2 (CXCL2; also known as MIP2) and TNF to promote neutrophil recruitment (41).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [41] Shen, 2015, Th17-Related Cytokines Contribute to Recall-Like Expansion/Effector Function of HMBPP-Specific Vγ2vδ2 T Cells After Mycobacterium Tuberculosis Infection or Vaccination, Eur J Immunol source

      The Introduction reports expansion of Vγ2Vδ2 T cells in lungs during mycobacterial infection, not proliferation of Vγ1+, Vγ4+, or Vγ6+ cells. Searches for those subsets and for CXCL2/MIP2, TNF, and neutrophil recruitment found no passage in our copy supporting the attributed mechanism; the Introduction mentions only general effects of IL-17 on neutrophils. Page numbers were not available in our copy. (LLM, conf=0.73)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    During lung infection, Vγ9Vδ2 γδ T cells are aggregated to produce IL-17 and IFN-γ, the former being the most important cytokine in TB protection.

    “During lung infection, Vγ9Vδ2 γδ T cells are aggregated to produce IL-17 and IFN-γ, the former being the most important cytokine in TB protection (43).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Dieli, 2013, Distribution, Function and Predictive Value of Tumor-Infiltrating γδ T Lymphocytes, Oncoimmunology source

      The Abstract (page unavailable) reports that melanoma-derived Vδ2 T-cell lines produced IFNγ. It does not address Vγ9Vδ2 cells accumulating during lung infection, their production of IL-17, or IL-17’s importance in TB protection. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    γδ T cells mostly reside within tissues, particularly in epithelial layers, where they might play tissue-protective or inflammatory roles.

    “γδ T cells mostly reside within tissues, particularly in epithelial layers, where they might play tissue-protective or inflammatory roles (5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Giri, 2021, Differentiation and Functional Plasticity of Gamma-Delta (γδ) T Cells Under Homeostatic and Disease Conditions, Mol Immunol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The human γ chain locus consists of four subgroups; VγI includes Vγ2, 3, 4, 5, and 8; among the three other Vγ subgroups, only Vγ9 (from the VγII group) is functional when using the nomenclature of Lefranc and Rabbitts.

    “Meanwhile, the human γ chain locus consists of four subgroups; VγI includes Vγ2, 3, 4, 5, and 8. Among the three other Vγ subgroups, only Vγ9 (from the VγII group) is functional when using the nomenclature of Lefranc and Rabbitts (4).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Lefranc, 1990, A Nomenclature to Fit the Organization of the Human T-Cell Receptor Gamma and Delta Genes, Res Immunol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Heilig and Tonegawa's nomenclature proposed in 1986 segregated mouse γδ T cells into six distinct subsets: Vγ1, Vγ2, Vγ4, Vγ5, Vγ6, and Vγ7.

    “Heilig and Tonegawa’s nomenclature proposed in 1986 segregated mouse γδ T cells into six distinct subsets: Vγ1, Vγ2, Vγ4, Vγ5, Vγ6, and Vγ7 (3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Heilig, 1986, Diversity of Murine Gamma Genes and Expression in Fetal and Adult T Lymphocytes, Nature source

  • May combine two claims.

    Premisecitation

    IL-17-producing γδ (γδ17) T cells have a beneficial role in steady-state skin physiology, and γδ17 T cells are also necessary for skin homeostasis.

    “Paradoxically, another study showed that IL-17-producing γδ (γδ17) T cells have a beneficial role in steady-state skin physiology, and γδ17 T cells are also necessary for skin homeostasis (Revised Figure 2 ).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In models of psoriasis and dermatitis, IL-17 is detrimental and is produced by dermal Vγ4+ and Vγ6+ γδ T cells rather than by DETCs.

    “However, in the models of psoriasis and dermatitis, IL-17 is detrimental and is produced by dermal Vγ4+ and Vγ6+ γδ T cells rather than by DETCs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Vγ3+ thymocytes are generated only during the early fetal stages of thymic development from E13 to E18 and migrate to the epidermis, where a defined homeostatic density is maintained throughout life by self-renewal.

    “Vγ3+ thymocytes are generated only during the early fetal stages of thymic development from E13 to E18 and migrate to the epidermis, where a defined homeostatic density is maintained throughout life by self-renewal (30).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Takagaki, 1989, Diversity of Gamma Delta T-Cell Receptors on Murine Intestinal Intra-Epithelial Lymphocytes, Nature source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Mouse γδ T cells can commit to effector cytokine production during thymic development; two main functional subsets are IFN-γ-producing γδ T cells and IL-17-producing γδ T cells.

    “On the other hand, mouse γδ T cells can commit to effector cytokine production during thymic development; two main functional subsets have been extensively described: IFN-γ-producing γδ T cells and IL-17-producing γδ T cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    IL-7 signaling promotes the development of IL-17-producing γδ T cells, whereas IL-15 and IL-2 induce IFN-γ secretion.

    “IL-7 signaling promotes the development of IL-17-producing γδ T cells, whereas IL-15 and IL-2 induce IFN-γ secretion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Unlike mouse skin epidermal T cells that only contain DETCs, the human epidermis contains both αβ T cells and γδ T cells, and Vδ1+ γδ T cells are localized in both the epidermis and dermis.

    “Unlike mouse skin epidermal T cells that only contain DETCs, the human epidermis contains both αβ T cells and γδ T cells, and Vδ1+ γδ T cells are localized in both the epidermis and dermis (40).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Lockhart, 2006, IL-17 Production is Dominated by Gammadelta T Cells Rather Than CD4 T Cells During Mycobacterium Tuberculosis Infection, J Immunol source

  • May combine two claims.

    Premisenone given

    Human Vδ1+ subsets are the major γδ T cells population in the intestine and skin, whereas Vδ3+ subsets are enriched in the liver and gut.

    “By contrast, human Vδ1+ subsets are the major γδ T cells population in the intestine and skin, whereas Vδ3+ subsets are enriched in the liver and gut.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    γδ T cells localized to the skin are mainly involved in maintaining tissue homeostasis and epithelial repair, maintaining epithelial barriers, and contributing to innate immunity.

    “γδ T cells localized to the skin are mainly involved in maintaining tissue homeostasis and epithelial repair, maintaining epithelial barriers, and contributing to innate immunity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Human γδ T cells are usually sub-divided based on the use of one of two variable regions of TCR-δ chains, Vδ1 or Vδ2.

    “Unlike murine γδ T cells, human γδ T cells are usually sub-divided based on the use of one of two variable regions of TCR-δ chains, which is Vδ1 or Vδ2.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    IFN-γ-producing γδ T cells express surface markers such as CD45RB and CD27.

    “(i) IFN-γ-producing γδ T cells express surface markers, such as CD45RB and CD27.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    γδ T cells are shaped by the microenvironment and exert tissue-specific functions depending on the signals they receive.

    “Accumulating evidence suggests that γδ T cells are shaped by the microenvironment and exert tissue-specific functions depending on the signals they receive.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The tissue-specific functions of γδ T cells, in terms of tissue retention and response to chemokines/cytokines, are not only related to the organ but also to species.

    “Finally, the tissue-specific functions of γδ T cells, in terms of tissue retention and response to chemokines/cytokines, are not only related to the organ but also to species.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Mouse γδ T cells in the uterus were tissue-resident memory γδ T cells expressing CD69 and expressed high levels of CCR6, GranzymeB, and CD107a.

    “In addition, mouse γδ T cells in the uterus were tissue-resident memory γδ T cells expressing CD69 and expressed high levels of CCR6, GranzymeB, and CD107a.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Similar to DETCs, human epidermal T cells produce keratinocyte growth factor (KGF) and insulin-like growth factor 1 (IGF1) and promote wound healing upon activation.

    “Similar to DETCs, human epidermal T cells produce keratinocyte growth factor (KGF) and insulin-like growth factor 1 (IGF1) and promote wound healing upon activation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Considerable numbers of Vγ4+ and Vγ6+ γδ T cells are present in mouse lungs, but their effect on lung tissue physiology is unclear.

    “Considerable numbers of Vγ4+ and Vγ6+ γδ T cells are present in mouse lungs, but their effect on lung tissue physiology is unclear (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Ribot, 2021, Gamma Delta T Cells in Tissue Physiology and Surveillance, Nat Rev Immunol source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    In humans, γδ T cells in blood display a quiescent state and migratory behavior reminiscent of naïve T cells.

    “In humans, γδ T cells in blood display a quiescent state and migratory behavior reminiscent of naiüve T cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    γδ T cells in the uterus were activated and fully expressed transcription factor RORγt.

    “Moreover, γδ T cells in the uterus were activated and fully expressed transcription factor RORγt.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The percentages of γδ T cells were significantly higher in the uterus than in peripheral blood, and most γδ T cells in mouse uterus were distributed in the endometrium.

    “A recent study has reported that the percentages of γδ T cells were significantly higher in the uterus than in peripheral blood, and most γδ T cells in mouse uterus were distributed in the endometrium (48).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Szekeres-Bartho, 2001, The Role of Gamma/Delta T Cells in the Feto-Maternal Relationship, Semin Immunol source

  • May combine two claims.

    Premisecitation

    The majority of γδ T cells in the uterus were memory cells with higher expression of CD44 and CD27 but lower expression of CD62L and CCR7 compared to those in the blood.

    “Further studies indicated that the majority of γδ T cells in the uterus were memory cells with higher expression of CD44 and CD27 but lower expression of CD62L and CCR7 compared to those in the blood (48).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Szekeres-Bartho, 2001, The Role of Gamma/Delta T Cells in the Feto-Maternal Relationship, Semin Immunol source

  • May combine two claims.

    Premisecitation

    Infected dendritic cells, through IL-23, can increase the production of IL-17 by Vγ4+ and Vγ6+ T cells and promote granuloma formation.

    “Studies have shown that infected dendritic cells, through IL-23, can increase the production of IL-17 by Vγ4+ and Vγ6+ T cells and promote granuloma formation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Human γδ T cells subsets rarely secrete IL-17, which is quite different from the mouse γδ T cells subset in the skin.

    “First, the human γδ T cells subsets rarely secrete IL-17, which was quite different from the mouse γδ T cells subset in the skin.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Mouse γδ T cells display tissue-specific degrees of IFN-γ and IL-17A production that appear to be regulated by factors present in the tissues, such as cytokines.

    “Although human γδ T cells deserve more research, mouse γδ T cells display tissue-specific degrees of IFN-γ and IL-17A production that appear to be regulated by factors present in the tissues, such as cytokines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In advanced non-small cell lung cancer, Vδ1 γδ T cells and Vδ1-Vδ2- γδ T cells are the main subpopulations of γδ T cells in the lung, and higher levels of intratumoral Vδ1 γδ T cells is a poor prognosis factor.

    “In advanced non-small cell lung cancer, Vδ1 γδ T cells and Vδ1-Vδ2-γδ T cells are the main subpopulations of γδ T cells in the lung, and higher levels of intratumoral Vδ1 γδ T cells is a poor prognosis factor (45).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Crawford, 2015, The Role of Seminal Plasma for Improved Outcomes During In Vitro Fertilization Treatment: Review of the Literature and Meta-Analysis, Hum Reprod Update source

  • May combine two claims.

    Premisenone given

    After a short time of activation, mouse γδ T cells in the uterus significantly expressed high levels of IL-17 but not IFN-γ, promoting the invasion of murine trophocytes.

    “After a short time of activation, mouse γδ T cells in the uterus significantly expressed high levels of IL-17 but not IFN-γ, promoting the invasion of murine trophocytes.”
    Quote in the paperSubstantial claim
46 of 46

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Human DETC equivalent is both denied and described as conserved

    Minor

    The human-skin section says there is no direct equivalent of mouse DETCs in human skin, then describes DETCs as a conserved expression in mouse and human skin.

  • Vγ5+ skin cells are placed in both the dermis and epidermis

    Minor

    The mouse-skin section places Vγ5+ cells in the dermis, whereas the development section says Vγ5Vδ1 cells are always in the epidermis.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Ribot, 2021, Gamma Delta T Cells in Tissue Physiology and Surveillance, Nat Rev Immunol, 21, 10.1038/s41577-020-00452-4 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Qu, G., Wang, S., Zhou, Z., Jiang, D., Liao, A., & Luo, J.
Affiliations
  • Huazhong University of Science and Technology (CN)
  • Jinan University (CN)
  • Wuhan Union Hospital (CN)
Corresponding author
  • Liao, Aihua
  • Luo, Jing
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-06-08
Volume
13
Pages
891687-891687
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2022.891687
PMC
PMC9215113
OpenAlex
W4281742159
Semantic Scholar
364f5db98f43d1ee420c42b7c1c6c67afaed8d58
Cited by
87
References
50
Citations by year
2026: 24 · 2025: 28 · 2024: 19 · 2023: 14 · 2022: 2
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords
γδ T cells, tissue-resident T cells, human-mouse comparison, tissue immunity, epithelium, skin, uterus, immune surveillance, tissue homeostasis
MeSH terms
Animals, Female, Homeostasis, Humans, Skin, T-Lymphocytes, Receptors, Antigen, T-Cell, gamma-delta, Lymphocyte Count, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-22.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-22.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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