Matches in SemOpenAlex for { <https://semopenalex.org/work/W2520612963> ?p ?o ?g. }
Showing items 1 to 89 of
89
with 100 items per page.
- W2520612963 abstract "Background Response Gene to Complement (RGC)−32 is an intracellular protein that plays a role in cell growth and promotes cell cycle activation and Akt phosphorylation. RGC-32 is also a downstream target of TGF-β in fibroblasts and renal proximal tubular cells and plays a role in renal fibrogenesis. In immune cells, RGC-32 is expressed by both T and B lymphocytes. Our prior studies showed that RGC-32 promotes Th17 differentiation of mouse CD4 T cells and is highly expressed in human IL-17 CD4 cells. Whether RGC-32 plays a role in the activation and differentiation of B cells and the development of autoimmunity is not known. We used WT and RGC-32 KO mice to determine whether lack of RGC-32 impairs B cell differentiation and activation and alters autoimmune parameters in the chronic graft versus host disease (cGVHD) model of lupus. Materials and methods B cells were cultured with lps, anti-CD40 mAb, IL-21 and IL-6, IL-4 or TGFβ and RGC-32 mRNA and protein expression was determined. TLR-dependent and T dependent B cell differentiation to plasma cells (PC) was induced with lps and with CD40mAb plus IL-4. cGVHD was induced with 100×10 6 Bm12 splenocytes injected into WT or RGC-32 KO recipients. Host B cell number and activation, anti-dsDNA Ab production, germinal centre (GC) B cell number and proliferation, PC number, expression of transcription factors IRF4 and Blimp1 were assessed at 2 and 4 weeks. Results RGC-32 mRNA was upregulated in B cells by lps, anti-CD40 mAb, IL-21 and IL-6. RGC-32 KO B cells failed to differentiate normally to PC as demonstrated by a 2-fold reduction in PC numbers generated after lps and anti-CD40+ IL-4 stimulation and impaired upregulation of Prdm1 and IRF4 mRNA. RGC-32 transcripts were upregulated in spleen cells from cGVHD mice and protein expression was detected in B cells and GC cells. RGC-32KO hosts displayed an attenuated autoimmune phenotype as demonstrated by: 1) decreased production of anti-dsDNA autoAb. 2) decreased number and proliferation of GC B cells. 3) decreased number of IgG anti-dsDNA secreting PC and 4) decreased IRF4 and Prdm1 mRNA expression. Conclusions These results suggest that expression of RGC-32 in B cells is critical for optimal GC proliferation, PC differentiation and autoantibody production in a murine model of lupus. These data support the idea that RGC-32 blockade has the potential to attenuate autoimmune parameters of cGVHD and possibly reverse abnormalities in the T and B cell pathways that contribute to lupus pathogenesis." @default.
- W2520612963 created "2016-09-23" @default.
- W2520612963 creator A5024891879 @default.
- W2520612963 creator A5028505493 @default.
- W2520612963 creator A5039973533 @default.
- W2520612963 creator A5063791039 @default.
- W2520612963 creator A5070794279 @default.
- W2520612963 creator A5077179478 @default.
- W2520612963 creator A5082433711 @default.
- W2520612963 date "2017-03-01" @default.
- W2520612963 modified "2023-09-24" @default.
- W2520612963 title "AI-05 Response gene to complement-32 promotes plasma cell differentiation and enhances lupus-like chronic graft versus host disease" @default.
- W2520612963 doi "https://doi.org/10.1136/lupus-2016-000179.5" @default.
- W2520612963 hasPublicationYear "2017" @default.
- W2520612963 type Work @default.
- W2520612963 sameAs 2520612963 @default.
- W2520612963 citedByCount "0" @default.
- W2520612963 crossrefType "journal-article" @default.
- W2520612963 hasAuthorship W2520612963A5024891879 @default.
- W2520612963 hasAuthorship W2520612963A5028505493 @default.
- W2520612963 hasAuthorship W2520612963A5039973533 @default.
- W2520612963 hasAuthorship W2520612963A5063791039 @default.
- W2520612963 hasAuthorship W2520612963A5070794279 @default.
- W2520612963 hasAuthorship W2520612963A5077179478 @default.
- W2520612963 hasAuthorship W2520612963A5082433711 @default.
- W2520612963 hasConcept C126322002 @default.
- W2520612963 hasConcept C153911025 @default.
- W2520612963 hasConcept C154317977 @default.
- W2520612963 hasConcept C159654299 @default.
- W2520612963 hasConcept C202751555 @default.
- W2520612963 hasConcept C203014093 @default.
- W2520612963 hasConcept C2776090121 @default.
- W2520612963 hasConcept C2776396001 @default.
- W2520612963 hasConcept C2776912625 @default.
- W2520612963 hasConcept C2778453870 @default.
- W2520612963 hasConcept C2779134260 @default.
- W2520612963 hasConcept C39347974 @default.
- W2520612963 hasConcept C55493867 @default.
- W2520612963 hasConcept C71924100 @default.
- W2520612963 hasConcept C86803240 @default.
- W2520612963 hasConcept C8891405 @default.
- W2520612963 hasConcept C95444343 @default.
- W2520612963 hasConcept C96926380 @default.
- W2520612963 hasConceptScore W2520612963C126322002 @default.
- W2520612963 hasConceptScore W2520612963C153911025 @default.
- W2520612963 hasConceptScore W2520612963C154317977 @default.
- W2520612963 hasConceptScore W2520612963C159654299 @default.
- W2520612963 hasConceptScore W2520612963C202751555 @default.
- W2520612963 hasConceptScore W2520612963C203014093 @default.
- W2520612963 hasConceptScore W2520612963C2776090121 @default.
- W2520612963 hasConceptScore W2520612963C2776396001 @default.
- W2520612963 hasConceptScore W2520612963C2776912625 @default.
- W2520612963 hasConceptScore W2520612963C2778453870 @default.
- W2520612963 hasConceptScore W2520612963C2779134260 @default.
- W2520612963 hasConceptScore W2520612963C39347974 @default.
- W2520612963 hasConceptScore W2520612963C55493867 @default.
- W2520612963 hasConceptScore W2520612963C71924100 @default.
- W2520612963 hasConceptScore W2520612963C86803240 @default.
- W2520612963 hasConceptScore W2520612963C8891405 @default.
- W2520612963 hasConceptScore W2520612963C95444343 @default.
- W2520612963 hasConceptScore W2520612963C96926380 @default.
- W2520612963 hasLocation W25206129631 @default.
- W2520612963 hasOpenAccess W2520612963 @default.
- W2520612963 hasPrimaryLocation W25206129631 @default.
- W2520612963 hasRelatedWork W1592667222 @default.
- W2520612963 hasRelatedWork W1909034893 @default.
- W2520612963 hasRelatedWork W1970893741 @default.
- W2520612963 hasRelatedWork W1977249247 @default.
- W2520612963 hasRelatedWork W1992312576 @default.
- W2520612963 hasRelatedWork W2063708965 @default.
- W2520612963 hasRelatedWork W2097479147 @default.
- W2520612963 hasRelatedWork W2102768377 @default.
- W2520612963 hasRelatedWork W2156087232 @default.
- W2520612963 hasRelatedWork W2160959184 @default.
- W2520612963 hasRelatedWork W2163206912 @default.
- W2520612963 hasRelatedWork W2274126705 @default.
- W2520612963 hasRelatedWork W2324063993 @default.
- W2520612963 hasRelatedWork W2346163061 @default.
- W2520612963 hasRelatedWork W2415867721 @default.
- W2520612963 hasRelatedWork W2740070809 @default.
- W2520612963 hasRelatedWork W2789292961 @default.
- W2520612963 hasRelatedWork W2944205407 @default.
- W2520612963 hasRelatedWork W2979028045 @default.
- W2520612963 hasRelatedWork W3182535168 @default.
- W2520612963 hasVolume "3" @default.
- W2520612963 isParatext "false" @default.
- W2520612963 isRetracted "false" @default.
- W2520612963 magId "2520612963" @default.
- W2520612963 workType "article" @default.