Invitro experiments demonstrated that collagen-specific T cell responses were significantly

Using immune histochemical staining with anti-B7-H3 mAb, we demonstrated that B7-H3 cell surface proteins could be detected, albeit in low levels, in the paw joints of normal mice, mainly expressed in osteoblasts on the surface cartilage. Importantly, the expression of B7-H3 is OG-L002 drastically upregulated in collagen-immunized mice and was correlated with the level of arthritic inflammation and bone destruction. The clinical symptoms of CIA and joint inflammation and destruction were markedly reduced in B7-H3 KO mice compare to the control mice. Invitro experiments demonstrated that collagen-specific T cell responses were significantly decreased and IFN-��, TNF and IL-17 cytokine production was accordingly reduced inB7-H3 KO mice. Our observations suggest that B7-H3 maybe an important mediator of pathogenesis and progression in inflammatory arthritis. Taken together, our results support the notion that B7-H3 differentially regulates T cell subsets by costimulating Th1 and Th17 while suppressing Th2 responses. This finding may explain, at least in part, the previously contradictory findings in various model systems. The molecular basis for this differential effect, however, has yet to be characterized. This will largely rely on the discovery of the B7-H3 counter-receptor and, in this regard, a different counter-receptor on these T cell subsets may cause the PF-573228 observed effects. Finally, our findings have important implications for the manipulation of B7-H3 in clinical applications to treat human disease. MicroRNAs are short non-coding RNA molecules that regulate gene expression by mediating the sequence-dependent degradation, or translational inhibition, of cognate mRNA transcripts. The pervasive regulatory roles of miRNAs have been well documented within the intra cellular environment; however, the biological roles of extra cellular miRNAs that circulate in blood are less well understood. Nevertheless, a growing number of studies have shown that these plasma/serum miRNAs may serve as non-invasive biomarkers for various clinical conditions, with the potential to guide therapeutic decisions by facilitating diagnosis, prognosis, and/or disease classification.

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