BACKGROUND & AIMS: Our previous studies have identified a B-cell subset that is induced under inflammatory conditions in T-cell receptor alpha knockout (TCRalphaKO) 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 TCRalphaKO mice, IL-12p35-deficient TCRalpha 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 TCRalphaKO mice. The expression of IL-12p35 was restored in the recipient B-cell-deficient TCRalpha double knockout (alphamicroDKO) 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 TCRalpha double knockout (alphap35DKO) mice compared with TCRalphaKO mice. In addition, transfer of MLN B cells from TCRalphaKO mice but not from alphap35DKO mice suppressed colitis in recipient alphamicroDKO 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.
BACKGROUND & AIMS: Our previous studies have identified a B-cell subset that is induced under inflammatory conditions in T-cell receptor alpha knockout (TCRalphaKO) 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 TCRalphaKO mice, IL-12p35-deficient TCRalpha 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 TCRalphaKO mice. The expression of IL-12p35 was restored in the recipient B-cell-deficient TCRalpha double knockout (alphamicroDKO) 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 TCRalpha double knockout (alphap35DKO) mice compared with TCRalphaKO mice. In addition, transfer of MLN B cells from TCRalphaKO mice but not from alphap35DKO mice suppressed colitis in recipient alphamicroDKO 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.
Authors: Shehzad Z Sheikh; Refaat A Hegazi; Taku Kobayashi; Joseph C Onyiah; Steven M Russo; Katsuyoshi Matsuoka; Antonia R Sepulveda; Fengling Li; Leo E Otterbein; Scott E Plevy Journal: J Immunol Date: 2011-03-28 Impact factor: 5.422
Authors: Michael McPherson; Bo Wei; Olga Turovskaya; Daisuke Fujiwara; Sarah Brewer; Jonathan Braun Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-07-10 Impact factor: 4.052