TY - JOUR
T1 - Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury
AU - Harrison, Oliver J.
AU - Linehan, Jonathan L.
AU - Shih, Han Yu
AU - Bouladoux, Nicolas
AU - Han, Seong Ji
AU - Smelkinson, Margery
AU - Sen, Shurjo K.
AU - Byrd, Allyson L.
AU - Enamorado, Michel
AU - Yao, Chen
AU - Tamoutounour, Samira
AU - Van Laethem, Francois
AU - Hurabielle, Charlotte
AU - Collins, Nicholas
AU - Paun, Andrea
AU - Salcedo, Rosalba
AU - O’Shea, John J.
AU - Belkaid, Yasmine
N1 - Funding Information:
We thank the National Institute of Allergy and Infectious Diseases (NIAID) animal facility staff; K. Holmes, E. Stregevsky, and T. Hawley (NIAID Flow Cytometry facility); G. Gutierrez-Cruz, S. Dell’Orso, and H.-W. Sun (NIAMS Genome Analysis Core facility); J. Kehr for editorial assistance; K. Beacht and S. Mistry for technical assistance; and I. Förster (University of Bonn) for generous provision of the anti–IL-18 hybridoma. f-MIIINA:H2-M3-tetramer reagents were obtained from the NIH Tetramer Core Facility. This study used the Office of Cyber Infrastructure and Computational Biology (OCICB) High Performance Computing (HPC) cluster at NIAID and the high-performance computational capabilities of the Biowulf Linux cluster at NIH. Supported by the NIAID Division of Intramural Research (ZIA-AI001115, ZIA-AI001132) (Y.B.); the Division of Intramural Research of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; ZIA-AR041159, ZIA-AR041167) (J.J.O.); a National Psoriasis Foundation Early Career Research Grant (O.J.H.); the National Institute of General Medical Sciences (NIGMS) Postdoctoral Research Associate (PRAT) fellowship program (J.L.L.); a European Molecular Biology Organization (EMBO) fellowship (S.T.); and Collège des Enseignants de Dermatologie Français, Société Française de Dermatologie, Philippe Foundation, and Fondation pour la Recherche Médicale (C.H.).
Publisher Copyright:
© The Authors.
PY - 2019/1/4
Y1 - 2019/1/4
N2 - Barrier tissues are primary targets of environmental stressors and are home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. We found 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 interleukin-18, these cells rapidly release type 2 cytokines, thereby acquiring contextual functions. Such acquisition of a type 2 effector program promotes tissue repair. 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 both local immunity and tissue adaptation to injury.
AB - Barrier tissues are primary targets of environmental stressors and are home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. We found 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 interleukin-18, these cells rapidly release type 2 cytokines, thereby acquiring contextual functions. Such acquisition of a type 2 effector program promotes tissue repair. 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 both local immunity and tissue adaptation to injury.
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U2 - 10.1126/science.aat6280
DO - 10.1126/science.aat6280
M3 - Article
C2 - 30523076
AN - SCOPUS:85058113593
SN - 0036-8075
VL - 363
JO - Science
JF - Science
IS - 6422
M1 - eaat6280
ER -