Inducible IL-12-Producing B Cells Regulate Th2-Mediated Intestinal Inflammation

Ken Sugimoto, Atsuhiro Ogawa, Yasuyo Shimomura, Kiyotaka Nagahama, Atsushi Mizoguchi, Atul K. Bhan

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background & Aims: Our previous studies have identified a B-cell subset that is induced under inflammatory conditions in T-cell receptor α knockout (TCRαKO) mice and contributes to the attenuation of colitis by producing interleukin (IL)-10. However, it is unclear whether IL-10-producing B cells directly or indirectly regulate inflammation. Methods: Cytokine production of purified mesenteric lymph node (MLN) B cells was examined by flow cytometric analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNase protection assay. To investigate the functional role of IL-12p70 in the pathogenesis of colitis in TCRαKO mice, IL-12p35-deficient TCRα double knockout mice were generated. Results: In the absence of B cells or IL-10, IL-12p35 expression was significantly down-regulated in the MLN of TCRαKO mice. The expression of IL-12p35 was restored in the recipient B-cell-deficient TCRα double knockout (αμDKO) mice by the transfer of B cells capable of producing IL-10. Notably, B cells predominantly produced IL-12p35 in the MLN through the help of IL-10-producing B cells. Functionally, IL-12 is involved in the regulation of the T-helper (Th) 2-mediated inflammation as indicated by the development of much more severe colitis in IL-12p35-deficient TCRα double knockout (αp35DKO) mice compared with TCRαKO mice. In addition, transfer of MLN B cells from TCRαKO mice but not from αp35DKO mice suppressed colitis in recipient αμDKO mice. Conclusions: These studies have identified a novel IL-12-producing regulatory B-cell subset that develops under Th2-mediated intestinal inflammatory conditions and in the presence of IL-10 and is involved in the regulation of intestinal inflammation.

Original languageEnglish
Pages (from-to)124-136
Number of pages13
JournalGastroenterology
Volume133
Issue number1
DOIs
Publication statusPublished - 06-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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