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MAIT cells are imprinted by the microbiota in early life and promote tissue repair
Open accessAbstract
Commensals rule the MAITrix: Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT cells recognize microbial small molecules presented by the major histocompatibility complex class Ib molecule MR1. MAIT cells are absent in germ-free mice, and the mechanisms by which microbiota control MAIT cell development are unknown (see the Perspective by Oh and Unutmaz). Legoux et al. show that, in mice, development of MAIT cells within the thymus is governed by the bacterial product 5-(2-oxopropylideneamino)-6- d -ribitylaminouracil, which rapidly traffics from the mucosa to the thymus, where it is captured by MR1 and presented to developing MAIT cells. Constantinides et al. report that MAIT cell induction only occurs during a limited, early-life window and requires exposure to defined microbes that produce riboflavin derivatives. Continual interactions between MAIT cells and commensals in the skin modulates tissue repair functions. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens. Science , this issue p. 494 , p. eaax6624 ; see also p. 419
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TL;DR
MAIT cells require a narrow early-life window of microbial exposure, especially riboflavin-synthesizing bacteria, to establish long-term tissue populations. In adult skin, these cells become a dominant IL-17A-producing, tissue-resident subset that responds to commensal antigens and cytokines and accelerates wound repair in mice.
Key findings
- MAIT cells were enriched in mouse skin, reaching up to 40% of αβ T cells, and averaged about 2% of CD3+ lymphocytes in human skin; germ-free mice had reduced MAIT cells across thymus, spleen, gut, skin, lungs, and liver.
- A defined five-species early-life community, or monocolonization with *Proteus mirabilis* alone, restored MAIT cell development in neonatal germ-free mice, whereas later-life exposure or adult conventionalization did not; topical 5-OP-RU also induced skin MAIT cells only when given early.
- Cutaneous MAIT cells were mostly double-negative, produced IL-17A rather than IFNγ, expressed type-17 genes including *Rorc*, *Il22*, *Il1r1*, and *Il23r*, and showed a tissue-repair transcriptional signature; IL-23 receptor deficiency reduced MAIT cell numbers, IL-18 blockade limited their expansion after *S. epidermidis*, and IL-1 receptor deficiency reduced IL-17A production.
- *S. epidermidis* lacking *ribD* failed to expand MAIT cells, while inducible MR1 deletion after development did not affect steady-state MAIT cells but prevented their response to *S. epidermidis*; in wounding experiments, MAIT-sufficient *Tcrd−/−* mice had longer epidermal tongues than MAIT-deficient *Mr1−/− Tcrd−/−* mice, and topical 5-OP-RU increased epidermal tongue length in wild-type mice.
Methods
- Mouse immunology study using SPF, germ-free, gnotobiotic, knockout, transgenic, parabiosis, and wound-healing models; early-life colonization was performed by oral gavage or topical skin association, with 16S rRNA sequencing and bacterial whole-genome sequencing to characterize communities and riboflavin synthesis genes.
- Immune populations were analyzed by flow cytometry, MR1 tetramer enrichment, confocal microscopy, RNA-sequencing, and single-cell RNA-sequencing; human skin specimens from elective surgery were digested and analyzed for MAIT cell frequency.
- Statistical comparisons used two-tailed unpaired Student’s t-tests; RNA-seq differential expression used DESeq2 with GO enrichment via Metascape, and scRNA-seq used Cell Ranger, CITE-seq-Count, and Seurat.
Limitations
- The paper states that how microbiota-derived riboflavin intermediates before and after birth contribute to human MAIT cell maturation and long-term tissue imprinting remains to be addressed.
- The functional wound-healing evidence is from murine punch-biopsy experiments, and MAIT cell function was tested in *Tcrd−/−* mice to reduce competition from γδ T cells, a setting the authors note is more relevant to human skin because human skin has fewer γδ T cells than mouse skin.
- Evident from the text: human data are limited mainly to skin MAIT cell frequency, and the study relies heavily on specific mouse models, defined bacterial strains, and early-life colonization conditions, so direct human causal tests of MAIT cell function are not provided.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The colonization of neonatal GF mice with our early-life microbial community induced MAIT cell development to the same extent observed in SPF mice harboring high MAIT cell frequencies (Fig. 1I).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, the monocolonization of neonatal GF mice with P. mirabilis, but not L. johnsonii, was sufficient to drive MAIT cell development (Fig. 1K).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In agreement with our observation that adult microbial colonization was insufficient to promote MAIT cell development (Fig. 1I), topical application of 5-OP-RU to the skin of adult GF mice failed to induce MAIT cells (Fig. 1L).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
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In the paper
“Cutaneous MAIT cells displayed a markedly different transcriptional profile (Figs. 2I–J & S2F–G).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene ontology (GO) enrichment analysis revealed that cutaneous MAIT cells express a transcriptional profile consistent with T cell activation, including leukocyte differentiation, migration and cell adhesion, cytokine production, and the ERK1/2 cascade, which is downstream of TCR signaling (Fig. 2C).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-23 receptor-deficient mice (Il23rgfp/gfp) exhibited fewer MAIT cells than WT animals (Figs. 2F–G & S2D–E)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“their ability to produce IL-17A was significantly decreased (Fig. 3N–O).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Skin-resident MAIT cells respond to cutaneous microbes in an IL-1- and IL-18-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, scRNA-seq confirmed that cutaneous MAIT cells express multiple genes associated with tissue repair, including Lgals3, F2r, Sdc1, and Npnt (Fig. 2J).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“S. epidermidis association promoted the expression of genes associated specifically with angiogenesis, including angiogenin (Ang) and Hgf (47, 48), as well as genes that more broadly promote tissue repair, like Ceacam1, Grn, Hmox1, Igf1, and Pdgfa (49–53) (Fig. 3R).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Skin-resident MAIT cells respond to cutaneous microbes in an IL-1- and IL-18-dependent manner
What the sources say
- Not checked yetcites [47] Bussolino F, Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 119, 629– 641 (1992). 1383237 PMC2289675 source
- Not checked yetcites [48] Miyake M, Goodison S, Lawton A, Gomes-Giacoia E, Rosser CJ, Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway. Oncogene 34, 890– 901 (2015). 24561529 PMC4317372 source
- Not checked yetcites [49] Toulon A, A role for human skin-resident T cells in wound healing. J Exp Med 206, 743– 750 (2009). 19307328 PMC2715110 source
- Not checked yetcites [50] He Z, Ong CH, Halper J, Bateman A, Progranulin is a mediator of the wound response. Nat Med 9, 225– 229 (2003). 12524533 source
- Not checked yetcites [51] LeBlanc S, CEACAM1 deficiency delays important wound healing processes. Wound Repair Regen 19, 745– 752 (2011). 22092845 source
- Not checked yetcites [52] Demaria M, An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell 31, 722– 733 (2014). 25499914 PMC4349629 source
- Not checked yetcites [53] Grochot-Przeczek A, Heme oxygenase-1 accelerates cutaneous wound healing in mice. PLoS One 4, e5803 (2009). 19495412 PMC2686151 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conversely, exposure later in life failed to promote MAIT cell development and accumulation within tissues (Fig. 1H–I)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with their IL-17A potential, MAIT cells expressed type-17-associated transcripts, including Il22 and Rorc, the gene for the transcription factor RORγt, as well as Il1r1 and Il23r, which encode receptors for interleukins IL-1 and IL-23, respectively (Fig. 2D).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Segmented filamentous bacteria (SFB), a known inducer of Th17 cells that lacks riboflavin synthesis enzymes (Figs. 1J & S1G) (29, 30), also failed to induce MAIT cells (Fig. 1K).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
What the sources say
- Not checked yetcites [29] Ivanov II, Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485– 498 (2009). 19836068 PMC2796826 source
- Not checked yetcites [30] Gaboriau-Routhiau V, The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677– 689 (2009). 19833089 source
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In the paper
“We found that MAIT cells from the skin and other barrier sites, such as the lungs and gut, were almost exclusively DN (Fig. 2H).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Intriguingly, MAIT cells were also enriched in GO terms associated with tissue repair (Fig. 2C)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As such, in mice with high MAIT cell frequencies, MAIT cells accounted for the largest proportion of IL-17A+ αβ T cells (Fig. 2B)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neutralization of IL-18 significantly reduced the MAIT cell response to S. epidermidis association (Fig. 3J–L)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Skin-resident MAIT cells respond to cutaneous microbes in an IL-1- and IL-18-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“A comparison of mice housed in conventional specific-pathogen-free (SPF) conditions to germ-free (GF) animals confirmed previous observations that the microbiota is necessary for the presence of MAIT cells in the thymus, spleen, and gut (17, 18), and extended this requirement for MAIT cells in the skin, lungs, and liver (Fig. 1B).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
What the sources say
- Not checked yetcites [17] Treiner E, Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422, 164– 169 (2003). 12634786 source
- Not checked yetcites [18] Koay HF, A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nat Immunol 17, 1300– 1311 (2016). 27668799 source
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In the paper
“MAIT cells expressed the highest levels of IL-23R among αβ T cells (Fig. 2E)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“found that MAIT cells predominantly resided near the interface of the dermis and epidermis, in close proximity to the basal layer (Fig. 5A).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MAIT cells promote tissue repair
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Application of antigen alone resulted in a significant increase of cutaneous IL-17A+ MAIT cells, with minimal effects on other T cells subsets (Figs. 4D–H & S4D–E).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the intestine harbors multiple bacterial families that are unable to generate riboflavin, riboflavin synthesis is highly conserved among skin commensals (Fig. 4A).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Tamoxifen treatment a week prior to the S. epidermidis association revealed that MR1-mediated antigen presentation is required for the MAIT cell response (Figs. 4I–J & S4R–S).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggested that MAIT cells respond to skin commensals locally, either via antigen recognition and/or cytokine stimulation.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Skin-resident MAIT cells respond to cutaneous microbes in an IL-1- and IL-18-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our results support the idea that in the context of homeostatic responses to the microbiota, the MAIT cell response is strictly TCR-dependent.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that MAIT cells promote tissue repair in the absence of compensatory responses by γδ T cells.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MAIT cells promote tissue repair
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, these results support the idea that production of riboflavin intermediates by S. epidermidis is required for local MAIT cell activation”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating that the microbially derived antigen 5-OP-RU was sufficient to promote wound healing in an intact host.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MAIT cells promote tissue repair
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- It may state two separate claims as one. 16
- Probably not a substantial claim. 7
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although MAIT cells were highly abundant within the skin, WT SPF mice housed in distinct cages showed striking variability in the proportion of MAIT cells among genetically identical animals, ranging from <5%−40% of αβ T cells (Fig. 1D–E). In contrast, animals in the same cage had similar frequencies of MAIT cells in the skin and other organs (Fig. 1E)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This analysis revealed that MAIT cells were highly enriched in the skin (Fig. 1B–C), where they comprised up to 40% of αβ T cells (Fig. 1D–E).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Topical application of 5-OP-RU was sufficient to induce a significant increase in the number of MAIT cells within the skin (Fig. 1L), without promoting the accumulation of other T cell subsets (Fig. S1J).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, MAIT cells were also enriched in human skin compared to the reported ~1% in peripheral blood (20), averaging ~2% of CD3+ lymphocytes (Fig. 1F).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Following stimulation, skin MAIT cells robustly produced IL-17A, but not IFNγ (Fig. 2A)”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed that in both cases, topical association expanded the cutaneous DN MAIT cell population and increased their production of IL-17A (Figs. 3A–D & S3B–D).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Skin-resident MAIT cells respond to cutaneous microbes in an IL-1- and IL-18-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“association with the S. epidermidis ΔribD mutant failed to induce a MAIT cell response (Fig. 4C), even though the CD8+ and γδ T cell responses were conserved (Fig. S4B–C).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MR1-mediated presentation of riboflavin metabolites is necessary and sufficient for MAIT cell recognition of skin commensals
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, early-life exposure to commensals that produce defined metabolites, or to microbially derived metabolites alone, is required for MAIT cell development and their presence later in life.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting the idea that homeostatic IL-23 contributes to MAIT cell development and/or accumulation within tissues.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Cutaneous MAIT cells express a type-17 transcriptional program and require homeostatic IL-23
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that microbial exposure in early life is required for the development of tissue MAIT cells, but not the thymic developmental stages.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Early-life exposure to riboflavin-synthesizing commensals is required for MAIT cell development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Unless otherwise noted, age- and sex-matched mice between 6 and 12 weeks of age were used for each experiment.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Dead cells were excluded from live samples using 4′, 6-diamidino-2-phenylindol (DAPI; Sigma-Aldrich), whereas either LIVE/DEAD Fixable Blue Dead Cell Stain Kit (Invitrogen Life Technologies) or Ghost Dye Violet 510 (Tonbo Biosciences) was used in fixed samples.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Flow cytometric analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“HTO were read in and assigned to the single cells and only singlets were used for further analysis leaving 585 cells.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Single-cell RNA-sequencing and analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, we show that MAIT cells are induced during a specific early-life window in response to riboflavin-synthesizing commensals, a phenomenon that permanently imprints the abundance of this subset in tissues.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Discussion
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In the paper
“Successful knockouts were confirmed by colony PCR and sequencing.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Generation of S. epidermidis mutant
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All staining was performed in the presence of purified anti-mouse CD16/32 and purified rat gamma globulin (Jackson ImmunoResearch).”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Flow cytometric analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, γδ T cells restrict the MAIT cell population at steady-state and constrain their response to commensals.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > MAIT cells promote tissue repair
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells with less than 900 or more than 3,000 gene counts, more than 5% mitochondrial contamination, or more than 10,000 RNA counts were filtered out, leaving 5,678 cells for downstream analysis.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Materials and Methods > Single-cell RNA-sequencing and analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, our work proposes that a central strategy utilized by the immune system to interact with the microbiota may be via the recognition of canonical microbially derived antigens by unconventional T cells, including MAIT cells, a dialogue that may play a dominant role in the control of host physiology.”
§ MAIT cells are imprinted by the microbiota in early life and promote tissue repair > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
Human T cells develop in utero.
“In contrast to mice, human T cells develop in utero supporting the hypothesis that such early MAIT cell imprinting may occur prior to birth.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The development and maturation of MAIT cells are dependent on microbiota, as demonstrated by reduced numbers of MAIT cells in GF mice, which can be restored through microbial colonization.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [693]
Citations
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
DADA2: High–resolution sample inference from Illumina amplicon data
Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., & Holmes, S. P. (2016) · Nature Methods · doi:10.1038/nmeth.3869 · Cited by 35,698
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Enzymatic assembly of DNA molecules up to several hundred kilobases
Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., & Smith, H. O. (2009) · Nature Methods · doi:10.1038/nmeth.1318 · Cited by 10,088
Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385
Self-citationInduction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409
Byrd, A. L., Belkaid, Y., & Segre, J. A. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.157 · Cited by 2,806
Self-citationAn Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045
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1 of the 81 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
The wound microbiota: microbial mechanisms of impaired wound healing and infection
Uberoi, A., McCready-Vangi, A. R., & Grice, E. A. (2024) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01035-z · Cited by 963
Microbiota and maintenance of skin barrier function
Harris-Tryon, T. A., & Grice, E. A. (2022) · Science · doi:10.1126/science.abo0693 · Cited by 672
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
Gut microbiome, liver immunology, and liver diseases
Wang, R., Tang, R., Li, B., Ma, X., Schnabl, B., & Tilg, H. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00592-6 · Cited by 466
Metadata
- Authors
- Constantinides, M. G., Link, V. M., Tamoutounour, S., Wong, A. C., Perez-Chaparro, P. J., Han, S.-J., Chen, Y. E., Li, K., Farhat, S., Weckel, A., Krishnamurthy, S. R., Vujkovic-Cvijin, I., Linehan, J. L., Bouladoux, N., Merrill, E. D., Roy, S., Cua, D. J., Adams, E. J., Bhandoola, A., Scharschmidt, T. C., Aubé, J., Fischbach, M. A., & Belkaid, Y.
- Affiliations
- National Institutes of Health (US)
- University of Pennsylvania (US)
- NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- Stanford University (US)
- University of North Carolina at Chapel Hill (US)
- University of California, San Francisco (US)
- University of Chicago (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Belkaid, Yasmine
- ORCID
- Constantinides, Michael G.
- Link, Verena M.
- Wong, Andrea C.
- Perez-Chaparro, P. Juliana
- Chen, Y. Erin
- Li, Kelin
- Weckel, Antonin
- Krishnamurthy, Siddharth R.
- Vujkovic-Cvijin, Ivan
- Linehan, Jonathan L.
- Bouladoux, Nicolas
- Merrill, E. Dean
- Roy, Sobhan
- Adams, Erin J.
- Bhandoola, Avinash
- Scharschmidt, Tiffany C.
- Aubé, Jeffrey
- Fischbach, Michael A.
- Belkaid, Yasmine
- Venue
- Science
- Published
- 2019-10-25
- Volume
- 366
- Issue
- 6464
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7603427
- OpenAlex
- W2981494076
- Cited by
- 567
- References
- 81
- Citations by year
- 2026: 57 · 2025: 93 · 2024: 82 · 2023: 81 · 2022: 92 · 2021: 76 · 2020: 80 · 2019: 4
- FWCI
- 25.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (R01-DK110174, DP1-DK113598, U19-AI111143)
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences
- Chan Zuckerberg Biohub
- Cancer Research Institute
- European Molecular Biology Organization
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (ZIA-AI001115, ZIA-AI001132)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- mucosal-associated invariant T cells, gut microbiota, MR1, riboflavin derivatives, thymus development, commensal bacteria, tissue repair, skin, mucosal immunity, microbial metabolites, germ-free mice
- MeSH terms
- Mucosal-Associated Invariant T Cells, Animals, Bacteria, Germ-Free Life, Humans, Interleukin-1, Mice, Inbred BALB C, Mice, Inbred C57BL, Riboflavin, Skin, Specific Pathogen-Free Organisms, Wound Healing, Histocompatibility Antigens Class I, Minor Histocompatibility Antigens, Mice, Knockout, Interleukin-17, Interleukin-18, Mice, Interleukin-23, Microbiota
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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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