Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury

Oliver J. Harrison; Jonathan L. Linehan; Han Yu Shih; Nicolas Bouladoux; Seong Ji Han; Margery Smelkinson; Shurjo K. Sen; Allyson L. Byrd; Michel Enamorado; Chen Yao; Samira Tamoutounour; Francois Van Laethem; Charlotte Hurabielle; Nicholas Collins; Andrea Paun; Rosalba Salcedo; John J. O’Shea; Yasmine Belkaid

doi:10.1126/science.aat6280

Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury

Oliver J. Harrison, Jonathan L. Linehan, Han Yu Shih, Nicolas Bouladoux, Seong Ji Han, Margery Smelkinson, Shurjo K. Sen, Allyson L. Byrd, Michel Enamorado, Chen Yao, Samira Tamoutounour, Francois Van Laethem, Charlotte Hurabielle, Nicholas Collins, Andrea Paun, Rosalba Salcedo, John J. O’Shea, Yasmine Belkaid

Research output: Contribution to journal › Article › peer-review

218 Scopus citations

Abstract

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.

Original language	English (US)
Article number	eaat6280
Journal	Science
Volume	363
Issue number	6422
DOIs	https://doi.org/10.1126/science.aat6280
State	Published - Jan 4 2019
Externally published	Yes

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Harrison, O. J., Linehan, J. L., Shih, H. Y., Bouladoux, N., Han, S. J., Smelkinson, M., Sen, S. K., Byrd, A. L., Enamorado, M., Yao, C., Tamoutounour, S., Van Laethem, F., Hurabielle, C., Collins, N., Paun, A., Salcedo, R., O’Shea, J. J., & Belkaid, Y. (2019). Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science, 363(6422), Article eaat6280. https://doi.org/10.1126/science.aat6280

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 2019, 'Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury', Science, vol. 363, no. 6422, eaat6280. https://doi.org/10.1126/science.aat6280

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title = "Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury",

abstract = "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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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.

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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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Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury

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