Cholera toxin enhances IL17 production by CD4+ T cells via cyclic AMP signaling pathway (163.5)

Abstract

Abstract Cholera toxin (CT) is one of the most potent mucosal adjuvants. It has been reported to improve antigen presentation as well as suppress resting T cell activation. Recently, CT was also reported to indirectly increase the Th17 response through elevating IL-6 production from dendritic cells. This result suggests a vital role of CT in mucosal immunity. The goal of our study is to understand how cholera toxin modulates the response of CD4 T cells. We found that CT can directly enhance IL-17 production by CD4+ T cells but decrease IFN-γ, TNF-α, IL2, and IL-10 production. In addition, CD4 T cells were treated with different cAMP-elevating agents, including CT B subunit and PKA inhibitors. We found that the effect of cholera toxin on Th17 response goes through a PKA-independent but cAMP signaling dependent pathway. A more detailed study of cAMP signaling is required to fully understand how cAMP signaling controls this Th17 response. Furthermore, CT may also prevent Th17 cells from becoming Th17/Th1 cells which are more pathogenic in Th17-mediated diseases. Whether cholera toxin or cAMP signaling constrains Th17-mediated pathology will be examined.