IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut.
Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10(-/-)) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19(+)CD25(+)CD1d(hi)IgM(hi)CD5(-)CD23(-)Tim-1(-)) of IL-10 producing Breg-like cells (Breg(IL-33)) was identified responsible for the protection. We demonstrated further that Breg(IL-33) isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10(-/-) mice. Our findings indicate an essential protective role, hence therapeutic potential, of Breg(IL-33) against mucosal inflammatory disorders in the gut.
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
Susanne
S
Sattler
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK; Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Guang-Sheng
GS
Ling
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
Damo
D
Xu
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Leonie
L
Hussaarts
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
Andreas
A
Romaine
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK; Department of Hepatobiliary Surgery, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
Hongzhi
H
Zhao
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
Liliane
L
Fossati-Jimack
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
Talat
T
Malik
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
H Terence
HT
Cook
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK.
Marina
M
Botto
Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Yu-Lung
YL
Lau
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Hermelijn H
HH
Smits
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
Foo Y
FY
Liew
Department of Medicine, Division of Immunology & Inflammation, Imperial College, London, UK; Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. Electronic address: fp.huang@imperial.ac.uk.
Fang-Ping
FP
Huang
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout
D015703:Antigens, CD; C556062:IL10 protein, mouse; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D016753:Interleukin-10
IBD; IL-10; IL-33; Mucosal inflammation; Regulatory B cell