Regulatory Lymphocytes and Intestinal Inflammation

被引:390
作者
Izcue, Ana [1 ]
Coombes, Janine L. [1 ]
Powrie, Fiona [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金
英国惠康基金;
关键词
intestinal flora; colitis; mucosa; intraepithelial lymphocytes (IEL); Foxp3; GROWTH-FACTOR-BETA; ALDRICH-SYNDROME PROTEIN; INVARIANT T-CELLS; TRANSCRIPTIONAL REPRESSOR BLIMP-1; IMMUNOLOGICAL SELF-TOLERANCE; TGF-BETA; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; LAMINA-PROPRIA; ULCERATIVE-COLITIS;
D O I
10.1146/annurev.immunol.021908.132657
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 immune system is pivotal in mediating the interactions between host and microbiota that shape the intestinal environment. Intestinal homeostasis arises from a highly dynamic balance between host protective immunity and regulatory mechanisms. This regulation is achieved by a number of cell populations acting through a set of shared regulatory pathways. In this review, we summarize the main lymphocyte subsets controlling immune responsiveness in the gut and their mechanisms of control, which involve maintenance of intestinal barrier function and suppression of chronic inflammation. CD4(+)Foxp3(+) T cells play a nonredundant role in the maintenance of intestinal homeostasis through IL-10- and TGF-beta-dependent mechanisms. Their activity is complemented by other T and B lymphocytes. Because breakdown in immune regulatory networks in the intestine leads to chronic inflammatory diseases of the gut, such as inflammatory bowel disease and celiac disease, regulatory lymphocytes are an attractive target for therapies of intestinal inflammation.
引用
收藏
页码:313 / 338
页数:26
相关论文
共 164 条
[11]   Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice [J].
Bjursten, M ;
Bland, PW ;
Willén, R ;
Hörnquist, EH .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (08) :2274-2283
[12]   Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease [J].
Brimnes, J ;
Allez, M ;
Dotan, I ;
Shao, L ;
Nakazawa, A ;
Mayer, L .
JOURNAL OF IMMUNOLOGY, 2005, 174 (09) :5814-5822
[13]   Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution [J].
Buckley, RH .
ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :625-655
[14]   RHuKGF ameliorates symptoms in DSS and CD4+CD45RBHi T cell transfer mouse models of inflammatory bowel disease [J].
Byrne, FR ;
Farrell, CL ;
Aranda, R ;
Rex, KL ;
Scully, S ;
Brown, HL ;
Flores, SA ;
Gu, LH ;
Danilenko, DM ;
Lacey, DL ;
Ziegler, TR ;
Senaldi, G .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2002, 282 (04) :G690-G701
[15]   Th3 cells in peripheral tolerance.: II.: TGF-β-transgenic Th3 cells rescue IL-2-deficient mice from autoimmunity [J].
Carrier, Yijun ;
Yuan, Jing ;
Kuchroo, Vijay K. ;
Weiner, Howard L. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (01) :172-178
[16]   Symbiotic bacteria direct expression of an intestinal bactericidal lectin [J].
Cash, Heather L. ;
Whitham, Cecilia V. ;
Behrendt, Cassie L. ;
Hooper, Lora V. .
SCIENCE, 2006, 313 (5790) :1126-1130
[17]   CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes [J].
Caudy, Amy A. ;
Reddy, Sreelatha T. ;
Chatila, Talal ;
Atkinson, John P. ;
Verbsky, James W. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (02) :482-487
[18]   The regulation of IgA class switching [J].
Cerutti, Andrea .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (06) :421-434
[19]   TGF-β released by apoptotic T cells contributes to an immunosuppressive milieu [J].
Chen, WJ ;
Frank, ME ;
Jin, WW ;
Wahl, SM .
IMMUNITY, 2001, 14 (06) :715-725
[20]   Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3 [J].
Chen, WJ ;
Jin, WW ;
Hardegen, N ;
Lei, KJ ;
Li, L ;
Marinos, N ;
McGrady, G ;
Wahl, SM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) :1875-1886