Regulatory T-cell therapy in Crohn's disease: challenges and advances

被引：131

作者：

Clough, Jennie N. ^{[1
,2
,3
]}

Omer, Omer S. ^{[1
,4
]}

Tasker, Scott ^{[5
]}

Lord, Graham M. ^{[1
,6
]}

Irving, Peter M. ^{[1
,4
]}

机构：

[1] Kings Coll London, Sch Immunol & Microbial Sci, London, England

[2] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London, England

[3] Kings Coll London, London, England

[4] Guys & St Thomas Hosp NHS Trust, Dept Gastroenterol, London, England

[5] Kings Coll London, Div Transplantat Immunol & Mucosal Biol, London, England

[6] Univ Manchester, Fac Biol Med & Hlth, Manchester, Lancs, England

来源：

GUT | 2020年 / 69卷 / 05期

基金：

英国医学研究理事会;

关键词：

INFLAMMATORY-BOWEL-DISEASE; EX-VIVO; IMMUNE DYSREGULATION; SELF-TOLERANCE; DIFFERENTIAL EXPRESSION; SUPPRESSIVE FUNCTION; ALLOGRAFT-REJECTION; ADOPTIVE TRANSFER; DENDRITIC CELLS; RETINOIC-ACID;

D O I：

10.1136/gutjnl-2019-319850

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

The prevalence of IBD is rising in the Western world. Despite an increasing repertoire of therapeutic targets, a significant proportion of patients suffer chronic morbidity. Studies in mice and humans have highlighted the critical role of regulatory T cells in immune homeostasis, with defects in number and suppressive function of regulatory T cells seen in patients with Crohn's disease. We review the function of regulatory T cells and the pathways by which they exert immune tolerance in the intestinal mucosa. We explore the principles and challenges of manufacturing a cell therapy, and discuss clinical trial evidence to date for their safety and efficacy in human disease, with particular focus on the development of a regulatory T-cell therapy for Crohn's disease.

引用

页码：942 / 952

页数：11

共 152 条

[51] Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity [J].

Goudy, Kevin ;

Aydin, Didem ;

Barzaghi, Federica ;

Gambineri, Eleonora ;

Vignoli, Marina ;

Mannurita, Sara Ciullini ;

Doglioni, Claudio ;

Ponzoni, Maurilio ;

Cicalese, Maria Pia ;

Assanelli, Andrea ;

Tommasini, Alberto ;

Brigida, Immacolata ;

Dellepiane, Rosa Maria ;

Martino, Silvana ;

Olek, Sven ;

Aiuti, Alessandro ;

Ciceri, Fabio ;

Roncarolo, Maria Grazia ;

Bacchetta, Rosa .

CLINICAL IMMUNOLOGY, 2013, 146 (03) :248-261

[52] Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study [J].

Grainge, Matthew J. ;

West, Joe ;

Card, Timothy R. .

LANCET, 2010, 375 (9715) :657-663

[53] The battle against immunopathology: infectious tolerance mediated by regulatory T cells [J].

Gravano, David M. ;

Vignali, Dario A. A. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2012, 69 (12) :1997-2008

[54] Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells [J].

Grossman, WJ ;

Verbsky, JW ;

Tollefsen, BL ;

Kemper, C ;

Atkinson, JP ;

Ley, TJ .

BLOOD, 2004, 104 (09) :2840-2848

[55] Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease [J].

GulwaniAkolkar, B ;

Akolkar, PN ;

Minassian, A ;

Pergolizzi, R ;

McKinley, M ;

Mullin, G ;

Fisher, S ;

Silver, J .

JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (06) :1344-1354

[56]

HAMANN A, 1994, J IMMUNOL, V152, P3282

[57] New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease? [J].

Harbige, James ;

Eichmann, Martin ;

Peakman, Mark .

JOURNAL OF AUTOIMMUNITY, 2017, 84 :12-20

[58] Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma [J].

Hartl, Dominik ;

Koller, Barbara ;

Mehlhorn, Alexander T. ;

Reinhardt, Dietrich ;

Nicolai, Thomas ;

Schendel, Dolores J. ;

Griese, Matthias ;

Krauss-Etschmann, Susanne .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (05) :1258-1266

[59] Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus [J].

He, Jing ;

Zhang, Xia ;

Wei, Yunbo ;

Sun, Xiaolin ;

Chen, Yaping ;

Deng, Jun ;

Jin, Yuebo ;

Gan, Yuzhou ;

Hu, Xin ;

Jia, Rulin ;

Xu, Chuanhui ;

Hou, Zhaohua ;

Leong, Yew Ann ;

Zhu, Lei ;

Feng, Jinhong ;

An, Yuan ;

Jia, Yuan ;

Li, Chun ;

Liu, Xu ;

Ye, Hua ;

Ren, Limin ;

Li, Ru ;

Yao, Haihong ;

Li, Yuhui ;

Chen, Shi ;

Zhang, Xuewu ;

Su, Yin ;

Guo, Jianping ;

Shen, Nan ;

Morand, Eric F. ;

Yu, Di ;

Li, Zhanguo .

NATURE MEDICINE, 2016, 22 (09) :991-+

[60] Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3γ1(Ala-Ala) [J].

Herold, KC ;

Burton, JB ;

Francois, F ;

Poumian-Ruiz, E ;

Glandt, M ;

Bluestone, JA .

JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (03) :409-418

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