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Cited by 85Chemokine receptors and signalingT-cell and B-cell ImmunologyDermatology and Skin Diseases

CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin

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Xia, Mingcan, Hu, Shaomin, Fu, Yaoyao, Jin, Wensen, Yi, Qiyi, Matsui, Yurika, Yang, Jie, McDowell, Mary Ann +3 more·2014·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2014.03.010PMC PMC4149943
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Abstract

Background CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. Objective We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation. Methods Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. Results CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin. Conclusion CCR10 is a critical regulator of skin immune homeostasis.

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  • CCR10 is a chemokine receptor expressed by most skin-resident T cells and is critical for their homeostatic establishment through interaction with CCL27 expressed by keratinocytes.

    “CCR10 is a chemokine receptor expressed by most skin-resident T cells and is critical for their homeostatic establishment through interaction with its ligand CCL27, expressed by keratinocytes.20,21”

    From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [20]

    The Results report that a majority of skin-resident αβ T cells in mice express CCR10; the Discussion says CCR10 is critical for their migration into and balanced maintenance in skin under homeostatic conditions. The Introduction identifies CCL27 as its ligand, but our copy does not establish that interaction with keratinocyte-expressed CCL27 causes this effect. For healthy human skin, the Results report significant percentages of CCR10-positive T cells, not most skin-resident T cells. No page numbers are available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Homozygous CCR10-KO/EGFP-KI mice have dysregulated skin-resident T cells compared to heterozygous mice, characterized mostly by reduction of CD8+ and CD4+ αβT cells but not IL-17A+ αβT or γδT cells.

    “Homozygous CCR10-KO/EGFP-KI (CCR10EGFP/EGFP, or CCR10−/− for simplicity) mice have dysregulated skin-resident T cells compared to heterozygous CCR10-KO/EGFP-KI (CCR10+/EGFP or CCR10+/−) mice, characterized mostly by the reduction of CD8+ and CD4+ αβT cells but not IL-17A+ αβT or γδT cells.20,22,23”

    From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [20]

    The Results section on imbalanced maintenance reports fewer skin CD8+ and CD4+ αβT cells in CCR10−/− mice than in heterozygous controls. It also reports more γδT cells in the dermis, but does not establish that γδT cells are not reduced across the skin as a whole. The impaired immune homeostasis section reports a higher percentage of IL-17A+ CD4+ cells, not whether their absolute number is unchanged. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 28

  1. [2]Sather BD Treuting P Perdue N Miazgowicz M Fontenot JD Rudensky AY Campbell DJ 2007 Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease J Exp Med 204 1335 1347 17548521 PMC2118615
  2. [3]Dudda JC Perdue N Bachtanian E Campbell DJ 2008 Foxp3+ regulatory T cells maintain immune homeostasis in the skin J Exp Med 205 1559 1565 18573908 PMC2442633
  3. [4]Gebhardt T Wakim LM Eidsmo L Reading PC Heath WR Carbone FR 2009 Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus Nat Immunol 10 524 530 19305395
  4. [5]Jiang X Clark RA Liu L Wagers AJ Fuhlbrigge RC Kupper TS 2012 Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity Nature 483 227 231 22388819 PMC3437663
  5. [6]Mackay LK Stock AT Ma JZ Jones CM Kent SJ Mueller SN Heath WR Carbone FR Gebhardt T 2012 Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation Proc Natl Acad Sci U S A 109 7037 7042 22509047 PMC3344960
  6. [7]Rosenblum MD Gratz IK Paw JS Lee K Marshak-Rothstein A Abbas AK 2012 Response to self antigen imprints regulatory memory in tissues Nature 480 538 542 22121024 PMC3263357
  7. [8]Zlotnik A Yoshie O 2012 The chemokine superfamily revisited Immunity 36 705 716 22633458 PMC3396424
  8. [9]Morales J Homey B Vicari AP Hudak S Oldham E Hedrick J Orozco R Copeland NG Jenkins NA McEvoy LM 1999 CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells Proc Natl Acad Sci U S A 96 14470 14475 10588729 PMC24460
  9. [10]Homey B Wang W Soto H Buchanan ME Wiesenborn A Catron D Muller A McClanahan TK Dieu-Nosjean MC Orozco R 2000 Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC) J Immunol 164 3465 3470 10725697
  10. [11]Jarmin DI Rits M Bota D Gerard NP Graham GJ Clark-Lewis I Gerard C 2000 Cutting edge: identification of the orphan receptor G-protein-coupled receptor 2 as CCR10, a specific receptor for the chemokine ESkine J Immunol 164 3460 3464 10725696
  11. [12]Homey B Alenius H Muller A Soto H Bowman EP Yuan W McEvoy L Lauerma AI Assmann T Bunemann E 2002 CCL27-CCR10 interactions regulate T cell-mediated skin inflammation Nat Med 8 157 165 11821900
  12. [13]Soler D Humphreys TL Spinola SM Campbell JJ 2003 CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking Blood 101 1677 1682 12406880
  13. [14]McCully ML Ladell K Hakobyan S Mansel RE Price DA Moser B 2012 Epidermis instructs skin homing receptor expression in human T cells Blood 120 4591 4598 23043070 PMC3790942
  14. [17]Chen L Lin SX Agha-Majzoub R Overbergh L Mathieu C Chan LS 2006 CCL27 is a critical factor for the development of atopic dermatitis in the keratin-14 IL-4 transgenic mouse model Int Immunol 18 1233 1242 16735375
  15. [18]Reiss Y Proudfoot AE Power CA Campbell JJ Butcher EC 2001 CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin J Exp Med 194 1541 1547 11714760 PMC2193675
  16. [19]Mirshahpanah P Li YY Burkhardt N Asadullah K Zollner TM 2008 CCR4 and CCR10 ligands play additive roles in mouse contact hypersensitivity Exp Dermatol 17 30 34 18095942
  17. [20]Tubo NJ McLachlan JB Campbell JJ 2011 Chemokine receptor requirements for epidermal T-cell trafficking Am J Pathol 178 2496 2503 21641376 PMC3124236
  18. [22]Hu S Yang K Yang J Li M Xiong N 2011 Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines Proc Natl Acad Sci U S A 108 E1035 1044 21969568 PMC3215018
  19. [23]Campbell JJ O’Connell DJ Wurbel MA 2007 Cutting Edge: Chemokine receptor CCR4 is necessary for antigen-driven cutaneous accumulation of CD4 T cells under physiological conditions J Immunol 178 3358 3362 17339428 PMC2575766
  20. [24]Nicolas L Sidjanski S Colle JH Milon G 2000 Leishmania major reaches distant cutaneous sites where it persists transiently while persisting durably in the primary dermal site and its draining lymph node: a study with laboratory mice Infect Immun 68 6561 6566 11083765 PMC97750
  21. [25]Kalia V Sarkar S Subramaniam S Haining WN Smith KA Ahmed R 2010 Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo Immunity 32 91 103 20096608
  22. [26]Hong K Chu A Ludviksson BR Berg EL Ehrhardt RO 1999 IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder J Immunol 162 7480 7491 10358203
  23. [27]Ma HL Liang S Li J Napierata L Brown T Benoit S Senices M Gill D Dunussi-Joannopoulos K Collins M 2008 IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation J Clin Invest 118 597 607 18202747 PMC2200300
  24. [28]Girardi M Lewis J Glusac E Filler RB Geng L Hayday AC Tigelaar RE 2002 Resident skin-specific gammadelta T cells provide local, nonredundant regulation of cutaneous inflammation J Exp Med 195 855 867 11927630 PMC2193718
  25. [29]Belkaid Y Piccirillo CA Mendez S Shevach EM Sacks DL 2002 CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity Nature 420 502 507 12466842
  26. [30]Francisco LM Salinas VH Brown KE Vanguri VK Freeman GJ Kuchroo VK Sharpe AH 2009 PD-L1 regulates the development, maintenance, and function of induced regulatory T cells J Exp Med 206 3015 3029 20008522 PMC2806460
  27. [32]Gebhardt T Whitney PG Zaid A Mackay LK Brooks AG Heath WR Carbone FR Mueller SN 2011 Different patterns of peripheral migration by memory CD4+ and CD8+ T cells Nature 477 216 219 21841802
  28. [33]Sharma R Sung SS Abaya CE Ju AC Fu SM Ju ST 2009 IL-2 regulates CD103 expression on CD4+ T cells in Scurfy mice that display both CD103-dependent and independent inflammation J Immunol 183 1065 1073 19553521 PMC2734909

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Sorted by citations

Authors
Xia, M., Hu, S., Fu, Y., Jin, W., Yi, Q., Matsui, Y., Yang, J., McDowell, M. A., Sarkar, S., Kalia, V., & Xiong, N.
Affiliations
  • Pennsylvania State University (US)
  • Anhui Medical University (CN)
  • University of Notre Dame (US)
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2014-09
Volume
134
Issue
3
Pages
634-644.e10
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2014.03.010
PMC
PMC4149943
OpenAlex
W2148561698
Cited by
85
References
5
Citations by year
2026: 8 · 2025: 6 · 2024: 5 · 2023: 13 · 2022: 9 · 2021: 15 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI071043, T32AI074551)
Topics
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
CCR10, CCL27, skin-resident T cells, regulatory T cells, effector T cells, skin immune homeostasis, skin inflammation, memory-like T cells, T cell migration, Leishmania infection, atopic dermatitis, psoriasis
MeSH terms
Animals, Cells, Cultured, Dermatitis, Atopic, Homeostasis, Humans, Immunity, Innate, Immunologic Memory, Inflammation, Mice, Inbred C57BL, Organ Specificity, Psoriasis, Skin, Autoimmunity, Up-Regulation, T-Lymphocyte Subsets, Mice, Knockout, T-Lymphocytes, Regulatory, Mice, Chemokine CCL27, Receptors, CCR10

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