New roles for IL-17-producing γδT cells in tissue homeostasis and pathology

Abstract

γδT cells are an unconventional population of T lymphocytes generated primarily early in life and enriched in non-lymphoid organs. A role for γδT cells in barrier tissue defense is well accepted in the field, but recent studies have shed light on potential roles in a variety of contexts ranging from cancer to thermogenesis and even memory formation. We explored the impact of γδT cells in models of autoimmunity and skeletal muscle regeneration. Germline knockout and TCR transgenic models implicated γδT cells in promoting tissue-specific autoimmune inflammation in a spontaneous model of T-cell- mediated autoimmunity. Ablation of γδT cells in this autoimmunity model at various time- points following neonatal life failed to ameliorate disease symptoms, suggesting that γδT cells might act very early in life to promote the eventual development of autoimmunity. In an alternate vein of research, we found that microbiota-dependent IL-17-producing γδT cells are enriched in skeletal muscle following cardiotoxin-induced injury. Ablation of γδT cells immediately prior to injury revealed that this population of cells promoted neutrophil recruitment, muscle stem cell proliferation, and subsequent tissue regeneration. The very processes that γδT cells promote as part of tissue repair are analogous to processes that are hallmarks of tissue pathology when they occur outside of a normal repair process. These observations highlight the importance of context when understanding the function of cell types and mediators and illustrate the importance of considering biological processes as part of larger networks.