Home LiteratureArticle Details
PMID: 23624556 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Deficiency in IL-17-committed Vγ4(+) γδ T cells in a spontaneous Sox13-mutant CD45.1(+) congenic mouse substrain provides protection from dermatitis.

Nature immunology ·Vol. 14 ·No. 6 ·2013-06-00 ·Pages 584-92

Gray EE, Ramírez-Valle F, Xu Y, Wu S, Wu Z, Karjalainen KE, Cyster JG

Abstract

Interleukin 17 (IL-17)-committed γδ T cells (γδT17 cells) participate in many immune responses, but their developmental requirements and subset specific functions remain poorly understood. Here we report that a commonly used CD45.1(+) congenic C57BL/6 mouse substrain is characterized by selective deficiency in Vγ4(+) γδT17 cells. This trait was due to a spontaneous mutation in the gene encoding the transcription factor Sox13 that caused an intrinsic defect in development of those cells in the neonatal thymus. The γδT17 cells migrated from skin to lymph nodes at low rates. In a model of psoriasis-like dermatitis, the Vγ4(+) γδT17 cell subset expanded considerably in lymph nodes and homed to inflamed skin. Sox13-mutant mice were protected from psoriasis-like skin changes, which identified a role for Sox13-dependent γδT17 cells in this inflammatory condition.

MeSH Terms
Animals Animals, Newborn Autoantigens/genetics,immunology,metabolism Cells, Cultured Dermatitis/genetics,immunology,metabolism Flow Cytometry Interleukin-17/genetics,immunology,metabolism Leukocyte Common Antigens/genetics,immunology,metabolism Lymph Nodes/immunology,metabolism,pathology Mice Mice, Congenic Mice, Inbred C57BL Mice, Inbred ICR Mice, Inbred NOD Mice, Knockout Mutation Psoriasis/genetics,immunology,metabolism Receptors, Antigen, T-Cell, gamma-delta/immunology,metabolism T-Lymphocyte Subsets/immunology,metabolism Thymus Gland/immunology,metabolism,pathology
Chemicals
Autoantigens Interleukin-17 Receptors, Antigen, T-Cell, gamma-delta Sox13 protein, mouse Leukocyte Common Antigens Ptprc protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gray Elizabeth E
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California, USA.
Ramírez-Valle Francisco
Xu Ying
Wu Shuang
Wu Zhihao
Karjalainen Klaus E
Cyster Jason G
References (50)
50 references, click to expand
  1. Epidermal CCR6+ γδ T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis.
    J Immunol. 2011 Nov 15;187(10):5026-31 PMID: 21984702
  2. Nonsense-mediated mRNA decay (NMD) mechanisms.
    Nat Struct Mol Biol. 2009 Feb;16(2):107-13 PMID: 19190664
  3. An HMG-box-containing T-cell factor required for thymocyte differentiation.
    Nature. 1995 Mar 2;374(6517):70-4 PMID: 7870176
  4. Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes.
    Nat Immunol. 2012 Apr 01;13(5):511-8 PMID: 22473038
  5. Cutting edge: spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF-beta 1-dependent mechanism.
    J Immunol. 2010 Feb 15;184(4):1675-9 PMID: 20061408
  6. Massive, sustained gammadelta T cell migration from the bovine skin in vivo.
    J Leukoc Biol. 2007 Apr;81(4):968-73 PMID: 17234682
  7. Subcapsular sinus macrophage fragmentation and CD169+ bleb acquisition by closely associated IL-17-committed innate-like lymphocytes.
    PLoS One. 2012;7(6):e38258 PMID: 22675532
  8. Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals.
    Immunity. 2009 Aug 21;31(2):321-30 PMID: 19682928
  9. Homing and cellular traffic in lymph nodes.
    Nat Rev Immunol. 2003 Nov;3(11):867-78 PMID: 14668803
  10. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors.
    Nature. 1988 Sep 29;335(6189):443-5 PMID: 2458531
  11. Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.
    Immunity. 2009 Oct 16;31(4):565-75 PMID: 19833086
  12. Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells.
    Eur J Immunol. 1999 Jun;29(6):2037-45 PMID: 10382767
  13. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice.
    J Clin Invest. 2010 May;120(5):1762-73 PMID: 20364087
  14. Diversity of murine gamma genes and expression in fetal and adult T lymphocytes.
    Nature. 1986 Aug 28-Sep 3;322(6082):836-40 PMID: 2943999
  15. Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.
    Immunity. 2011 Oct 28;35(4):596-610 PMID: 21982596
  16. T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis.
    J Immunol. 2011 Apr 1;186(7):3946-52 PMID: 21339363
  17. Gammadelta T cells in EAE: early trafficking events and cytokine requirements.
    Eur J Immunol. 2009 Jun;39(6):1516-26 PMID: 19384874
  18. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk.
    J Clin Invest. 2012 Nov;122(11):3965-76 PMID: 23064362
  19. Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice.
    J Clin Invest. 2012 Jun;122(6):2252-6 PMID: 22546855
  20. Comparison of mouse Ly5a and Ly5b leucocyte common antigen alleles.
    Dev Immunol. 1991;1(4):243-54 PMID: 1822988
  21. Recirculating memory T cells are a unique subset of CD4+ T cells with a distinct phenotype and migratory pattern.
    J Immunol. 2013 Feb 1;190(3):970-6 PMID: 23255361
  22. Marking and quantifying IL-17A-producing cells in vivo.
    PLoS One. 2012;7(6):e39750 PMID: 22768117
  23. Cutaneous immunosurveillance by self-renewing dermal gammadelta T cells.
    J Exp Med. 2011 Mar 14;208(3):505-18 PMID: 21339323
  24. Cutting edge: Identification of a motile IL-17-producing gammadelta T cell population in the dermis.
    J Immunol. 2011 Jun 1;186(11):6091-5 PMID: 21536803
  25. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
    Immunity. 2009 Aug 21;31(2):331-41 PMID: 19682929
  26. Interleukin 7 (IL-7) selectively promotes mouse and human IL-17-producing γδ cells.
    Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17549-54 PMID: 23047700
  27. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation.
    Nat Immunol. 2009 Jul;10(7):786-93 PMID: 19503106
  28. The Sox-13 gene: structure, promoter characterization, and chromosomal localization.
    Genomics. 1999 Apr 15;57(2):301-5 PMID: 10198172
  29. Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis.
    J Immunol. 2011 Sep 1;187(5):2783-93 PMID: 21813772
  30. Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells.
    Immunity. 2011 Jul 22;35(1):59-68 PMID: 21737317
  31. Exacerbation of collagen-induced arthritis by oligoclonal, IL-17-producing gamma delta T cells.
    J Immunol. 2007 Oct 15;179(8):5576-83 PMID: 17911645
  32. Different gamma delta T-cell receptors are expressed on thymocytes at different stages of development.
    Proc Natl Acad Sci U S A. 1989 Jan;86(2):631-5 PMID: 2463632
  33. Cloning of Ly-5 cDNA.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7360-3 PMID: 3864163
  34. CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.
    Eur J Immunol. 2009 Dec;39(12):3488-97 PMID: 19830744
  35. SCART scavenger receptors identify a novel subset of adult gammadelta T cells.
    J Immunol. 2008 Aug 1;181(3):1710-6 PMID: 18641307
  36. Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.
    Arch Dermatol. 2004 Dec;140(12):1490-5 PMID: 15611427
  37. Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice.
    Cell. 1993 Jul 16;74(1):143-56 PMID: 8334701
  38. Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice.
    J Clin Invest. 2010 Mar;120(3):883-93 PMID: 20179354
  39. Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production.
    J Immunol. 2007 Apr 1;178(7):4466-72 PMID: 17372004
  40. Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos.
    BMC Dev Biol. 2009 Sep 09;9:49 PMID: 19740427
  41. Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave.
    Immunity. 2012 Jul 27;37(1):48-59 PMID: 22770884
  42. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice.
    J Clin Invest. 2009 Aug;119(8):2317-29 PMID: 19662682
  43. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.
    Nature. 2004 Jan 22;427(6972):355-60 PMID: 14737169
  44. Monitoring cellular movement in vivo with photoconvertible fluorescence protein "Kaede" transgenic mice.
    Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10871-6 PMID: 18663225
  45. Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
    Science. 2007 Jan 12;315(5809):230-3 PMID: 17218525
  46. Cloning and characterization of mouse mSox13 cDNA.
    Gene. 1998 Feb 27;208(2):201-6 PMID: 9524265
  47. Critical role of TCF-1 in repression of the IL-17 gene.
    PLoS One. 2011;6(9):e24768 PMID: 21935461
  48. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.
    J Immunol. 2009 May 1;182(9):5836-45 PMID: 19380832
  49. T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis.
    J Exp Med. 2008 May 12;205(5):1173-86 PMID: 18443226
  50. Identification of CD25+ gamma delta T cells as fetal thymus-derived naturally occurring IL-17 producers.
    J Immunol. 2008 Nov 1;181(9):5940-7 PMID: 18941182
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2585
Published
2013-06-00
Epub
2013-00-28
Pages
584-92
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3660499
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R01 AI045073 · United States
NIAMS NIH HHS · T32 AR007175 · United States
NIAID NIH HHS · AI045073 · United States
External Links
PubMed source DOI: 10.1038/ni.2585 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2