The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells

被引：176

作者：

Vegran, Frederique ^{[1
,2
]}

Berger, Helene ^{[1
,2
]}

Boidot, Romain ^{[3
]}

Mignot, Gregoire ^{[1
,2
]}

Bruchard, Melanie ^{[1
,2
]}

Dosset, Magalie ^{[1
,2
]}

Chalmin, Fanny ^{[1
,2
]}

Rebe, Cedric ^{[1
,2
,3
]}

Derangere, Valentin ^{[1
,2
]}

Ryffel, Bernhard ^{[4
,5
,6
]}

Kato, Masashi ^{[7
]}

Prevost-Blondel, Armelle ^{[8
,9
,10
]}

Ghiringhelli, Francois ^{[1
,2
,3
]}

Apetoh, Lionel ^{[1
,2
,3
]}

机构：

[1] INSERM, U866, Dijon, France

[2] Univ Bourgogne, Fac Med, Dijon, France

[3] Ctr Georges Francois Leclerc, Dijon, France

[4] CNRS, F-45071 Orleans, France

[5] Univ Orleans, UMR7355, Orleans, France

[6] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa

[7] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Nagoya, Aichi 4648601, Japan

[8] CNRS, UMR 8104, Paris, France

[9] INSERM, U1016, Paris, France

[10] Paris Descartes Univ, Cochin Inst, Paris, France

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 08期

关键词：

T-CELLS; METASTATIC MELANOMA; IFN-GAMMA; IMMUNE-RESPONSES; MOUSE MODEL; FACTOR PU.1; TGF-BETA; ACTIVATION; IL-9; PHOSPHORYLATION;

D O I：

10.1038/ni.2925

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The T(H)9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of T(H)9 cells and dictated their anticancer properties. Under T(H)9-skewing conditions, interleukin 1 beta (IL-1 beta) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of II9 and II21 and enhanced secretion of the cytokines IL-9 and IL-21 from T(H)9 cells. Furthermore, IL-1 beta-induced T(H)9 cells exerted potent anticancer functions in an IRF1- and IL-21-dependent manner. Our findings thus identify IRF1 as a target for controlling the function of T(H)9 cells.

引用

页码：758 / +

页数：11

共 50 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].

Adachi, O ;

Kawai, T ;

Takeda, K ;

Matsumoto, M ;

Tsutsui, H ;

Sakagami, M ;

Nakanishi, K ;

Akira, S .

IMMUNITY, 1998, 9 (01) :143-150

[2] MyD88, an adapter protein involved in interleukin-1 signaling [J].

Burns, K ;

Martinon, F ;

Esslinger, C ;

Pahl, H ;

Schneider, P ;

Bodmer, JL ;

Di Marco, F ;

French, L ;

Tschopp, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (20) :12203-12209

[3] The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation [J].

Chang, Hua-Chen ;

Sehra, Sarita ;

Goswami, Ritobrata ;

Yao, Weiguo ;

Yu, Qing ;

Stritesky, Gretta L. ;

Jabeen, Rukhsana ;

McKinley, Carl ;

Ahyi, Ayele-Nati ;

Han, Ling ;

Nguyen, Evelyn T. ;

Robertson, Michael J. ;

Perumal, Narayanan B. ;

Tepper, Robert S. ;

Nutt, Stephen L. ;

Kaplan, Mark H. .

NATURE IMMUNOLOGY, 2010, 11 (06) :527-U98

[4] Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling [J].

Chung, Yeonseok ;

Chang, Seon Hee ;

Martinez, Gustavo J. ;

Yang, Xuexian O. ;

Nurieva, Roza ;

Kang, Hong Soon ;

Ma, Li ;

Watowich, Stephanie S. ;

Jetten, Anton M. ;

Tian, Qiang ;

Dong, Chen .

IMMUNITY, 2009, 30 (04) :576-587

[5] Follicular Helper CD4 T Cells (TFH) [J].

Crotty, Shane .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :621-663

[6] IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+ IL-10+ Foxp3- effector T cells [J].

Dardalhon, Valerie ;

Awasthi, Amit ;

Kwon, Hyoung ;

Galileos, George ;

Gao, Wenda ;

Sobel, Raymond A. ;

Mitsdoerffer, Meike ;

Strom, Terry B. ;

Elyaman, Wassim ;

Ho, I-Cheng ;

Khoury, Samia ;

Oukka, Mohamed ;

Kuchroo, Vijay K. .

NATURE IMMUNOLOGY, 2008, 9 (12) :1347-1355

[7] JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].

DARNELL, JE ;

KERR, IM ;

STARK, GR .

SCIENCE, 1994, 264 (5164) :1415-1421

[8]

Dudley ME, 2002, SCIENCE, V298, P850, DOI 10.1126/science.1076514

[9] IFN-γ represses IL-4 expression via IRF-1 and IRF-2 [J].

Elser, B ;

Lohoff, M ;

Kock, S ;

Giaisi, M ;

Kirchhoff, S ;

Krammer, PH ;

Li-Weber, M .

IMMUNITY, 2002, 17 (06) :703-712

[10] Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma [J].

Eyles, Jo ;

Puaux, Anne-Laure ;

Wang, Xiaojie ;

Toh, Benjamin ;

Prakash, Celine ;

Hong, Michelle ;

Tan, Tze Guan ;

Zheng, Lin ;

Ong, Lai Chun ;

Jin, Yi ;

Kato, Masashi ;

Prevost-Blondel, Armelle ;

Chow, Pierce ;

Yang, Henry ;

Abastado, Jean-Pierre .

JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (06) :2030-2039

← 1 2 3 4 5 →