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One in every three adults in the United States has hypertension, and the underlying cause of most of these cases is unknown. Therefore, it is imperative to continue the study of mechanisms involved in the pathogenesis of hypertension. Decades ago, studies speculated that elements of an autoimmune response were associated with the development of hypertension based, in part, on the presence of circulating autoantibodies in hypertensive patients. In the past decade, a growing number of studies have been published supporting the concept that self-antigens and the subsequent activation of the adaptive immune system promote the development of hypertension. This manuscript will provide a brief review of the evidence supporting a role for the immune system in the development of hypertension, studies that implicate both cell-mediated and humoral immunity, and the relevance of understanding blood pressure control in an autoimmune disease model with hypertension. [ABSTRACT FROM AUTHOR]

Improper regulation of B cell responses leads to excessive production of antibodies and contributes to the development of autoimmune disease. T helper 17 (Th17) cells also drive the development of autoimmune disease, but the role of B cells in shaping Th17 cell-mediated immune responses, as well as the reciprocal regulation of B cell responses by IL-17 family cytokines, remains unclear. The aim of this study was to characterize the regulation of IL-17A and IL-17F in a model of T cell-dependent B cell activation. Stimulation of primary human B cell and peripheral blood mononuclear cell (BT) co-cultures with α-IgM and a non-mitogenic concentration of superantigens for three days promoted a Th17 cell response as evidenced by increased expression of Th17-related gene transcripts, including Il17f, Il21, Il22, and Il23r, in CD4 T cells, as well as the secretion of IL-17A and IL-17F protein. We tested the ability of 144 pharmacologic modulators representing 91 different targets or pathways to regulate IL-17A and IL-17F production in these stimulated BT co-cultures. IL-17A production was found to be preferentially sensitive to inhibition of the PI3K/mTOR pathway, while prostaglandin EP receptor agonists, including PGE2, increased IL-17A concentrations. In contrast, the production of IL-17F was inhibited by PGE2, but selectively increased by TLR2 and TLR5 agonists. These results indicate that IL-17A regulation is distinct from IL-17F in stimulated BT co-cultures and that this co-culture approach can be used to identify pathway mechanisms and novel agents that selectively inhibit production of IL-17A or IL-17F. [ABSTRACT FROM AUTHOR]