The Syk-NFAT-IL-2 Pathway in Dendritic Cells Is Required for Optimal Sterile Immunity Elicited by Alum Adjuvants.

ABSTRACT: Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca²⁺ mobilization, and calcineurin-dependent activation of NF

SUBMITTER: Khameneh HJ 

PROVIDER: S-EPMC5164880 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature