TNF-α blockade induces IL-10 expression in human CD4+ T cells

被引：0

作者：

Hayley G. Evans

Urmas Roostalu

Gina J. Walter

Nicola J. Gullick

Klaus S. Frederiksen

Ceri A. Roberts

Jonathan Sumner

Dominique L. Baeten

Jens G. Gerwien

Andrew P. Cope

Frederic Geissmann

Bruce W. Kirkham

Leonie S. Taams

机构：

[1] Centre for Molecular and Cellular Biology of Inflammation (CMCBI),Division of Immunology

[2] Infection and Inflammatory Disease,Department of Clinical Immunology and Rheumatology

[3] King’s College London,Academic Department of Rheumatology

[4] Biopharmaceuticals Research Unit,Department of Rheumatology

[5] Inflammation Biology,undefined

[6] Novo Nordisk A/S,undefined

[7] Academic Medical Centre/University of Amsterdam,undefined

[8] King's College London,undefined

[9] Guy’s and St Thomas’ NHS Trust,undefined

[10] Present address: Nuffield Department of Clinical Neurosciences,undefined

[11] Weatherall Institute of Molecular Medicine,undefined

[12] John Radcliffe Hospital,undefined

[13] University of Oxford,undefined

[14] Oxford OX3 9DS,undefined

[15] UK,undefined

[16] Present address: Institute of Inflammation and Repair,undefined

[17] Michael Smith Bldg,undefined

[18] Oxford Road,undefined

[19] University of Manchester,undefined

[20] Manchester M13 9PL,undefined

[21] UK,undefined

[22] Present address: Department of Rheumatology,undefined

[23] King’s College Hospital NHS Trust,undefined

[24] London SE5 9RS,undefined

[25] UK,undefined

来源：

Nature Communications | / 5卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

引用

共 50 条

[21] Interleukin-21 maintains the expression of CD16 on monocytes via the production of IL-10 by human naive CD4+ T cells
Liu, Yun
Yang, Binyan
Ma, Jiangjun
Wang, Hui
Huang, Fengyu
Zhang, Jianping
Chen, Hui
Wu, Changyou
CELLULAR IMMUNOLOGY, 2011, 267 (02) : 102 - 108
[22] CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production
Barthlott, T
Moncrieffe, H
Veldhoen, M
Atkins, CJ
Christensen, J
O'Garra, A
Stockinger, B
INTERNATIONAL IMMUNOLOGY, 2005, 17 (03) : 279 - 288
[23] IRF4 regulates IL-10 gene expression in CD4+ T cells through differential nuclear translocation
Lee, Choong-Gu
Hwang, Won
Maeng, Ki-Eun
Kwon, Ho-Keun
So, Jae-Seon
Sahoo, Anupama
Lee, Sung Haeng
Park, Zee Yong
Im, Sin-Hyeog
CELLULAR IMMUNOLOGY, 2011, 268 (02) : 97 - 104
[24] CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10
Annacker, O
Pimenta-Araujo, R
Burlen-Defranoux, O
Barbosa, TC
Cumano, A
Bandeira, A
JOURNAL OF IMMUNOLOGY, 2001, 166 (05): : 3008 - 3018
[25] IL-10 production by CD4+ effector T cells: a mechanism for self-regulation
Jankovic, D.
Kugler, D. G.
Sher, A.
MUCOSAL IMMUNOLOGY, 2010, 3 (03) : 239 - 246
[26] Differential Regulation of the Let-7 Family of MicroRNAs in CD4+ T Cells Alters IL-10 Expression
Swaminathan, Sanjay
Suzuki, Kazuo
Seddiki, Nabila
Kaplan, Warren
Cowley, Mark J.
Hood, Chantelle L.
Clancy, Jennifer L.
Murray, Daniel D.
Mendez, Catalina
Gelgor, Linda
Anderson, Ben
Roth, Norman
Cooper, David A.
Kelleher, Anthony D.
JOURNAL OF IMMUNOLOGY, 2012, 188 (12): : 6238 - 6246
[27] TNF-α and IL-10 Control CXCL13 Expression in Human Macrophages
Bellamri, Nessrine
Viel, Roselyne
Morzadec, Claudie
Lecureur, Valerie
Joannes, Audrey
de Latour, Bertrand
Llamas-Gutierrez, Francisco
Wollin, Lutz
Jouneau, Stephane
Vernhet, Laurent
JOURNAL OF IMMUNOLOGY, 2020, 204 (09): : 2492 - 2502
[28] IL-10 produced by activated human B cells regulates CD4+ T-cell activation in vitro
Bouaziz, Jean-David
Calbo, Sebastien
Maho-Vaillant, Maud
Saussine, Anne
Bagot, Martine
Bensussan, Armand
Musette, Philippe
EUROPEAN JOURNAL OF IMMUNOLOGY, 2010, 40 (10) : 2686 - 2691
[29] IL-33 induces IL-9 production in human CD4+ T cells
Blom, L.
Hansen, A.
Poulsen, L.
ALLERGY, 2011, 66 : 121 - 121
[30] Association of IL-10 Gene Polymorphism With IL-10 Secretion by CD4 and T Regulatory Cells in Human Leprosy
Tarique, Mohammad
Naz, Huma
Saini, Chaman
Suhail, Mohd
Shankar, Hari
Khanna, Neena
Sharma, Alpana
FRONTIERS IN IMMUNOLOGY, 2020, 11

← 1 2 3 4 5 →