STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles

Abstract A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expressi...

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Autores principales:	Jalila Alshekaili, Rochna Chand, Cindy Eunhee Lee, Susan Corley, Kristy Kwong, Ilenia Papa, David A. Fulcher, Katrina L. Randall, Jennifer W. Leiding, Cindy S. Ma, Marc R. Wilkins, Gulbu Uzel, Chris C. Goodnow, Carola G. Vinuesa, Stuart G. Tangye, Matthew C. Cook
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2eb94b50da340409764c3fb20783667
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spelling	oai:doaj.org-article:e2eb94b50da340409764c3fb207836672021-12-02T11:41:03ZSTAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles10.1038/s41598-018-21389-82045-2322https://doaj.org/article/e2eb94b50da340409764c3fb207836672018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21389-8https://doaj.org/toc/2045-2322Abstract A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.Jalila AlshekailiRochna ChandCindy Eunhee LeeSusan CorleyKristy KwongIlenia PapaDavid A. FulcherKatrina L. RandallJennifer W. LeidingCindy S. MaMarc R. WilkinsGulbu UzelChris C. GoodnowCarola G. VinuesaStuart G. TangyeMatthew C. CookNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jalila Alshekaili Rochna Chand Cindy Eunhee Lee Susan Corley Kristy Kwong Ilenia Papa David A. Fulcher Katrina L. Randall Jennifer W. Leiding Cindy S. Ma Marc R. Wilkins Gulbu Uzel Chris C. Goodnow Carola G. Vinuesa Stuart G. Tangye Matthew C. Cook STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
description	Abstract A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.
format	article
author	Jalila Alshekaili Rochna Chand Cindy Eunhee Lee Susan Corley Kristy Kwong Ilenia Papa David A. Fulcher Katrina L. Randall Jennifer W. Leiding Cindy S. Ma Marc R. Wilkins Gulbu Uzel Chris C. Goodnow Carola G. Vinuesa Stuart G. Tangye Matthew C. Cook
author_facet	Jalila Alshekaili Rochna Chand Cindy Eunhee Lee Susan Corley Kristy Kwong Ilenia Papa David A. Fulcher Katrina L. Randall Jennifer W. Leiding Cindy S. Ma Marc R. Wilkins Gulbu Uzel Chris C. Goodnow Carola G. Vinuesa Stuart G. Tangye Matthew C. Cook
author_sort	Jalila Alshekaili
title	STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
title_short	STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
title_full	STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
title_fullStr	STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
title_full_unstemmed	STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
title_sort	stat3 regulates cytotoxicity of human cd57+ cd4+ t cells in blood and lymphoid follicles
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e2eb94b50da340409764c3fb20783667
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STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles

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