IL-10-producing Regulatory B10 Cells Inhibit Intestinal Injury in a Mouse Model

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2011 Feb 2

PMID 21281806

Citations 80

Authors

Koichi Yanaba

Ayumi Yoshizaki

Yoshihide Asano

Takafumi Kadono

Thomas F Tedder

Shinichi Sato

Affiliations

Soon will be listed here.

Abstract

B cells mediate multiple functions that influence immune and inflammatory responses. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to immediate intestinal injury. Dextran sulfate sodium-induced intestinal injury serves as an experimental animal model for human ulcerative colitis. The contribution of B cells to DSS-induced intestinal injury is unclear. In this study, we show that DSS-induced intestinal injury was more severe in CD19-deficient (CD19(-/-)) mice than in wild-type mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1% to 2% of splenic B220(+) cells in wild-type mice. Remarkably, adoptive transfer of these B10 cells from wild-type mice reduced inflammation in CD19(-/-) mice in an IL-10-dependent manner. These results demonstrate that IL-10 production from regulatory B10 cells regulates DSS-induced intestinal injury. These findings may provide new insights and therapeutic approaches for treating ulcerative colitis.

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References

Linton P, Bautista B, Biederman E, Bradley E, Harbertson J, Kondrack R . Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo. J Exp Med. 2003; 197(7):875-83. PMC: 2193894. DOI: 10.1084/jem.20021290. View

Bouaziz J, Yanaba K, Venturi G, Wang Y, Tisch R, Poe J . Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice. Proc Natl Acad Sci U S A. 2007; 104(52):20878-83. PMC: 2409235. DOI: 10.1073/pnas.0709205105. View

Taguchi T, McGhee J, Coffman R, Beagley K, Eldridge J, Takatsu K . Analysis of Th1 and Th2 cells in murine gut-associated tissues. Frequencies of CD4+ and CD8+ T cells that secrete IFN-gamma and IL-5. J Immunol. 1990; 145(1):68-77. View

Wirtz S, Neufert C, Weigmann B, Neurath M . Chemically induced mouse models of intestinal inflammation. Nat Protoc. 2007; 2(3):541-6. DOI: 10.1038/nprot.2007.41. View

Sato S, Ono N, Steeber D, Pisetsky D, Tedder T . CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J Immunol. 1996; 157(10):4371-8. View

Constant S, Schweitzer N, West J, Ranney P, Bottomly K . B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo. J Immunol. 1995; 155(8):3734-41. View

Venturi G, Tu L, Kadono T, Khan A, Fujimoto Y, Oshel P . Leukocyte migration is regulated by L-selectin endoproteolytic release. Immunity. 2003; 19(5):713-24. DOI: 10.1016/s1074-7613(03)00295-4. View

Fillatreau S, Sweenie C, McGeachy M, Gray D, Anderton S . B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002; 3(10):944-50. DOI: 10.1038/ni833. View

Yanaba K, Bouaziz J, Haas K, Poe J, Fujimoto M, Tedder T . A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008; 28(5):639-50. DOI: 10.1016/j.immuni.2008.03.017. View

10.

Cooper H, Murthy S, Shah R, Sedergran D . Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69(2):238-49. View

11.

Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg R, Bhan A . Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002; 16(2):219-30. DOI: 10.1016/s1074-7613(02)00274-1. View

12.

Haas K, Poe J, Steeber D, Tedder T . B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity. 2005; 23(1):7-18. DOI: 10.1016/j.immuni.2005.04.011. View

13.

Spencer N, Daynes R . IL-12 directly stimulates expression of IL-10 by CD5+ B cells and IL-6 by both CD5+ and CD5- B cells: possible involvement in age-associated cytokine dysregulation. Int Immunol. 1997; 9(5):745-54. DOI: 10.1093/intimm/9.5.745. View

14.

Hibi T, Ogata H . Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006; 41(1):10-6. DOI: 10.1007/s00535-005-1744-3. View

15.

Meijerink J, Mandigers C, van de Locht L, Tonnissen E, Goodsaid F, Raemaekers J . A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR. J Mol Diagn. 2001; 3(2):55-61. PMC: 1910699. DOI: 10.1016/S1525-1578(10)60652-6. View

16.

Murthy S, Cooper H, Shim H, Shah R, Ibrahim S, Sedergran D . Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci. 1993; 38(9):1722-34. DOI: 10.1007/BF01303184. View

17.

Yanaba K, Hamaguchi Y, Venturi G, Steeber D, St Clair E, Tedder T . B cell depletion delays collagen-induced arthritis in mice: arthritis induction requires synergy between humoral and cell-mediated immunity. J Immunol. 2007; 179(2):1369-80. DOI: 10.4049/jimmunol.179.2.1369. View

18.

Matsushita T, Horikawa M, Iwata Y, Tedder T . Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010; 185(4):2240-52. PMC: 3717968. DOI: 10.4049/jimmunol.1001307. View

19.

Rudolph U, Finegold M, Rich S, Harriman G, Srinivasan Y, Brabet P . Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet. 1995; 10(2):143-50. DOI: 10.1038/ng0695-143. View

20.

Matsushita T, Yanaba K, Bouaziz J, Fujimoto M, Tedder T . Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 2008; 118(10):3420-30. PMC: 2542851. DOI: 10.1172/JCI36030. View