CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm

被引:359
作者
Hirahara, Kiyoshi [1 ,2 ]
Nakayama, Toshinori [2 ,3 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[2] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[3] Japan Agcy Med Res & Dev AMED, AMED CREST, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
关键词
epigenetics; memory T(h)2 cells; pathogenic T(h)2 (T(path)2) cells; T-cell plasticity; T(h)1/T(h)2 paradigm; TRANSCRIPTION FACTOR; AIRWAY INFLAMMATION; GENE-EXPRESSION; T(H)17 CELLS; TGF-BETA; LINEAGE COMMITMENT; ATOPIC-DERMATITIS; CLUSTER-ANALYSIS; SUPER-ENHANCERS; TYPE-2; IMMUNITY;
D O I
10.1093/intimm/dxw006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD4(+) T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (T(h)1) and T(h)2 cells, unexpected increases in the numbers of CD4(+) T-cell subsets, including T(h)17, T(h)9, T follicular-helper (T-fh) and T-regulatory (T-reg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type T(h)2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the T(h)1/T(h)2 balance. To this end, we propose another model-the pathogenic T-helper population disease-induction model-as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases.
引用
收藏
页码:163 / 171
页数:9
相关论文
共 137 条
[1]   Regulatory T cells: recommendations to simplify the nomenclature [J].
Abbas, Abul K. ;
Benoist, Christophe ;
Bluestone, Jeffrey A. ;
Campbell, Daniel J. ;
Ghosh, Sankar ;
Hori, Shohei ;
Jiang, Shuiping ;
Kuchroo, Vijay K. ;
Mathis, Diane ;
Roncarolo, Maria Grazia ;
Rudensky, Alexander ;
Sakaguchi, Shimon ;
Shevach, Ethan M. ;
Vignali, Dario A. A. ;
Ziegler, Steve F. .
NATURE IMMUNOLOGY, 2013, 14 (04) :307-308
[2]   Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[3]   IL-22 Fate Reporter Reveals Origin and Control of IL-22 Production in Homeostasis and Infection [J].
Ahlfors, Helena ;
Morrison, Peter J. ;
Duarte, Joao H. ;
Li, Ying ;
Biro, Judit ;
Tolaini, Mauro ;
Di Meglio, Paola ;
Potocnik, Alexandre J. ;
Stockinger, Brigitta .
JOURNAL OF IMMUNOLOGY, 2014, 193 (09) :4602-4613
[4]   TH17 and TH22 cells: A confusion of antimicrobial response with tissue inflammation versus protection [J].
Akdis, Muebeccel ;
Palomares, Oscar ;
van de Veen, Willem ;
van Splunter, Marloes ;
Akdis, Cezmi A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2012, 129 (06) :1438-1449
[5]   TH17 Cells in Asthma and COPD [J].
Alcorn, John F. ;
Crowe, Christopher R. ;
Kolls, Jay K. .
ANNUAL REVIEW OF PHYSIOLOGY, 2010, 72 :495-516
[6]   Regulation of Th2 differentiation and Il4 locus accessibility [J].
Ansel, K. Mark ;
Djuretic, Ivana ;
Tanasa, Bogdan ;
Rao, Anjana .
ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :607-656
[7]   CXCR3, CXCL10 and type 1 diabetes [J].
Antonelli, Alessandro ;
Ferrari, Silvia Martina ;
Corrado, Alda ;
Ferrannini, Ele ;
Fallahi, Poupak .
CYTOKINE & GROWTH FACTOR REVIEWS, 2014, 25 (01) :57-65
[8]   A Distinct Function of Regulatory T Cells in Tissue Protection [J].
Arpaia, Nicholas ;
Green, Jesse A. ;
Moltedo, Bruno ;
Arvey, Aaron ;
Hemmers, Saskia ;
Yuan, Shaopeng ;
Treuting, Piper M. ;
Rudensky, Alexander Y. .
CELL, 2015, 162 (05) :1078-1089
[9]   Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses [J].
Arsenio, Janilyn ;
Kakaradov, Boyko ;
Metz, Patrick J. ;
Kim, Stephanie H. ;
Yeo, Gene W. ;
Chang, John T. .
NATURE IMMUNOLOGY, 2014, 15 (04) :365-+
[10]   Interleukin-17 up-regulation of nitric oxide production in human osteoarthritis cartilage [J].
Attur, MG ;
Patel, RN ;
Abramson, SB ;
Amin, AR .
ARTHRITIS AND RHEUMATISM, 1997, 40 (06) :1050-1053