Differential effects of cyclosporine A and TGFβ1 on IgE- versus IL-33-mediated mast cell activation (HYP3P.407)

• Published in: The Journal of immunology (1950) Vol. 192; no. 1_Supplement; pp. 54 - 54.19
• Main Authors: Chernushevich, Oksana, Ndaw, Victor, Ryan, John
• Format: Journal Article
• Language: English
• Published: 01.05.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.54.19

Abstract Cyclosporine A (CsA), a potent calcineurin antagonist and immunosuppressant, is known to inhibit IgE-mediated mast cell activation. The present research investigates the role of this drug in suppressing IL-33-mediated mast cell activation. IL-33 is a novel cytokine of IL-1 family that elicits mast cells to produce inflammatory cytokines independently of IgE-FcεRI signals. We have found that low concentrations of CsA (10nM) are capable of suppressing IgE-mediated cytokine production by 50-80% in mouse bone marrow-derived mast cells. By comparison, IL-33-mediated secretion of TNF, IL-6, and MCP-1 was unaffected by CsA under these conditions. These results were consistent among mast cells derived from C57BL/6, 129Sv, C3H, and A/J mouse strains. We have previously reported that TGFβ1 inhibits IgE-mediated cytokine production. Our current experiments showed that TGFβ1 similarly antagonizes IL-33-induced cytokine secretion, and that CsA does not enhance this effect. These data demonstrate that mast cell activation by IL-33, thought to be a key regulator of innate immunity, is responsive to TGFβ1-mediated suppression, but relatively resistant to CsA effects. Understanding how mast cells are regulated by innate signals will shed light on many inflammatory diseases.