Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury.
Harrison OJ, Linehan JL, Shih HY, Bouladoux N, Han SJ, Smelkinson M, Sen SK, Byrd AL, Enamorado M, Yao C, Tamoutounour S, Van Laethem F, Hurabielle C, Collins N, Paun A, Salcedo R, O'Shea JJ, Belkaid Y
Science. Jan 2019
COMMENT: Because of the extraordinary number of antigens expressed by the microbiota, a significant fraction of skin-resident T cells are expected to be commensal-specific, accumulating over time in response to successive exposure to new commensals. The skin is the first interface with the environment and it is in charge of orchestating the tissue protection from stressor as injuries, invasive pathogens or impaires immunoregulation. This protection is mediated by rapid and coordinated responses specific for each kind of stressors.
Here, we explore the unique features of commensal-specific T cells and how their distinct wiring might promote physiological or pathological tissue adaptation.
Here, we show that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type-17 program associated with a poised type-2 state. Thus, in the context of injury and exposure to inflammatory mediators such as IL-18, these cells rapidly release type-2 cytokines, thereby acquiring contextual functions. Notably, such acquisition of a type-2 effector program promotes tissue repair.
Here, we show that adaptation of tissue to injuries can also be mediated by immunity to the microbio-ta, a fundamental but poorly understood class of immunity. Notably, we found that homeostatic immunity to bacteria or fungal commensals is characterized by the co-expression of paradoxical programs, allowing commensal-specific T cells, when entering and persisting within tissues, to adopt a type-17 program compatible with tissue homeostasis and immunity while maintaining a type-2-poised state. As such, in the context of injury and consequent exposure to in-flammatory mediators and cognate antigens, commensal-specific T cells rapidly release type-2 cytokines, allowing these cells to exert pleiotropic and contextual functions in-cluding tissue repair. Thus, we describe a tissue checkpoint that relies on the remarkable plasticity and adaptability of tissue-resident commensal-specific T cells.