Mouse Anti-Human IFN-γ Hybridoma [IFN-2036]

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered to be critical regulators of thymic inflammation in AChR-MG patients. However, Th17 cells are functionally heterogeneous and circulating Th17 subsets are incompletely understood in AChR-MG patients. Here, we studied characteristics of Th17 subsets in peripheral blood from treatment-naive AChR-MG patients, patients treated with immunosuppressants, as well as healthy controls. We found increased frequencies of circulating Th1-like Th17 (Th1/17) (IFN-gamma + IL-17 + CD4 + CD3+) cells, which declined earlier than conventional Th17 (IFN-gamma - IL-17 + CD4 + CD3+) cells in patients who respond well to immunosuppression treatment. Additionally, circulating Th1/17 cell frequencies were found to correlate positively with disease severity. Further, compared to conventional Th17 cells, Th1/17 cells showed an elevated expression of IFNG, TBX21, IL23R, CSF2, and a reduced expression of AHR and IL10. Taken together, our results suggest circulating Th1/17 cells may serve as a biomarker of disease severity and provide a strong rationale for early intervention in AChR-MG patients.

Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1 beta, IL-6, IFN-gamma, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted.