PRJNA486019
Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury
Barrier tissues are primary targets of environmental stressors and home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. Here, we show that skin-resident commensal-specific T cells harbor a paradoxical program allowing acquisition of a type-17 program compatible with tissue homeostasis and immunity, while maintaining a poised type-2 state. Thus, in the context of injury and exposure to defined alarmins and inflammatory mediators such as IL-18, these cells rapidly release type-2 cytokines, thereby acquiring pleiotropic and contextual functions. Aberrant type-2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote tissue adaptation to injury, a feature that also bears pathogenic potential.