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

Nat Immunol. 2013 Jun;14(6):584-92. doi: 10.1038/ni.2585. Epub 2013 Apr 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Autoantigens / metabolism
  • Cells, Cultured
  • Dermatitis / genetics
  • Dermatitis / immunology*
  • Dermatitis / metabolism
  • Flow Cytometry
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mutation
  • Psoriasis / genetics
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Thymus Gland / pathology

Substances

  • Autoantigens
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sox13 protein, mouse
  • Leukocyte Common Antigens
  • Ptprc protein, mouse