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10.4049/jimmunol.1601427 http://scihub22266oqcxt.onion/10.4049/jimmunol.1601427 C5113143!5113143!27742832     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27742832&cmd=llinks): Failed to open stream: HTTP request failed! 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Small molecule inhibition of Rab7 impairs B cell class-switching and plasma cell survival to dampen the autoantibody response in murine lupus |pdf=|usr=}}{{27742832}} gab.com Text Small molecule inhibition of Rab7 impairs B cell class-switching and plasma cell survival to dampen the autoantibody response in murine lupus JO: J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=27742832 #FOAvip IgG autoantibodies mediate pathology in systemic lupus patients and lupus-prone mice. Here we showed that the class-switched IgG autoantibody response in MRL/Faslpr/lpr and C57/Sle1Sle2Sle2 mice was blocked by the CID 1067700 compound, which specifically targeted Rab7, an endosome-localized small GTPase that was upregulated in activated human and mouse lupus B cells, leading to prevention of disease development and extension of life-span. These were associated with decreased IgG-expressing B cells and plasma cells, but unchanged numbers and functions of myeloid cells and T cells. The Rab7 inhibitor suppressed T cell-dependent and T cell-independent antibody responses, but did not affect T cell-mediated clearance of Chlamydia infection, consistent with a B cell-specific role of Rab7. Indeed, B cells and plasma cells were inherently sensitive to Rab7 gene knockout or Rab7 activity inhibition in class-switching and survival, respectively, while proliferation/survival of B cells and generation of plasma cells were not affected. Impairment of NF-?B activation upon Rab7 inhibition, together with the rescue of B cell class-switching and plasma cell survival by enforced NF-?B activation, indicated that Rab7 mediates these processes by promoting NF-?B activation, likely through signal transduction on intracellular membrane structures. Thus, a single Rab7-inhibiting small molecule can target two stages of B cell differentiation to dampen the pathogenic autoantibody response in lupus. Twit Text FOAVip Small molecule inhibition of Rab7 impairs B cell class-switching and plasma cell survival to dampen the autoantibody response in murine lupus ????J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=27742832 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27742832 #FOAvip English Wikipedia <ref>{{Cite pmid|27742832}}</ref> Small molecule inhibition of Rab7 impairs B cell class-switching and plasma cell survival to dampen the autoantibody response in murine lupus #MMPMID27742832 Lam T; Kulp DV; Wang R; Lou Z; Taylor J; Rivera CE; Yan H; Zhang Q; Wang Z; Zan H; Ivanov DN; Zhong G; Casali P; Xu Z J Immunol 2016[Nov]; 197 (10): 3792-805 PMID27742832show ga IgG autoantibodies mediate pathology in systemic lupus patients and lupus-prone mice. Here we showed that the class-switched IgG autoantibody response in MRL/Faslpr/lpr and C57/Sle1Sle2Sle2 mice was blocked by the CID 1067700 compound, which specifically targeted Rab7, an endosome-localized small GTPase that was upregulated in activated human and mouse lupus B cells, leading to prevention of disease development and extension of life-span. These were associated with decreased IgG-expressing B cells and plasma cells, but unchanged numbers and functions of myeloid cells and T cells. The Rab7 inhibitor suppressed T cell-dependent and T cell-independent antibody responses, but did not affect T cell-mediated clearance of Chlamydia infection, consistent with a B cell-specific role of Rab7. Indeed, B cells and plasma cells were inherently sensitive to Rab7 gene knockout or Rab7 activity inhibition in class-switching and survival, respectively, while proliferation/survival of B cells and generation of plasma cells were not affected. Impairment of NF-?B activation upon Rab7 inhibition, together with the rescue of B cell class-switching and plasma cell survival by enforced NF-?B activation, indicated that Rab7 mediates these processes by promoting NF-?B activation, likely through signal transduction on intracellular membrane structures. Thus, a single Rab7-inhibiting small molecule can target two stages of B cell differentiation to dampen the pathogenic autoantibody response in lupus. äSmall molecule inhibition of Rab7 impairs B cell class-switching and p(epmc).pdf DeepDyve Pubget Overpricing