PPARγAgonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

Abstract

Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγ are members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγ is activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγ has also been associated with B cells. The present review addresses these issues by placing PPARγ agonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

The multifaceted factor peroxisome proliferator-activated receptor γ (PPARγ) in metabolism, immunity, and cancer

“…T cells can be controlled by PPARc (Hontecillas and Bassaganya-Riera 2007;Guri et al 2010). Similar to the effects in T cells, PPARc activation in B cells is antiproliferative, but the effects are not consistent with those reported in the literature (da Rocha Junior et al 2013). Given that various autoimmune diseases are associated with the aberrant activation of adaptive immunity, further understanding of PPARc effects in the context of immune diseases will be required.…”

“…In addition to the roles in the innate immune system, several studies have demonstrated that PPARc also tunes adaptive immune responses (da Rocha Junior et al 2013;Kidani and Bensinger 2012). PPARc negatively regulates T cell survival and activation by inhibiting IL-2 production.…”

“…PPARc negatively regulates T cell survival and activation by inhibiting IL-2 production. PPARc is also involved in the balance of Th1/Th2 by increasing Th2 cytokine and IL-4 production but decreasing IFN-c and Th1 cytokine production, although Th2 preference by PPARc activation can be dependent on the cell type and selective ligand (Tontonoz and Spiegelman 2008;da Rocha Junior et al 2013). PPARc activation also impairs Th17 cell development and affects Th17-dependent autoimmune diseases such as experimental autoimmune encephalomyelitis, inflammatory bowel disease, and arthritis (Straus and Glass 2007;Klotz et al 2009).…”

PPARγ ligands and their therapeutic applications: a patent review (2008 – 2014)

“…Macrophages expressing PPARg regulate inflammatory responses by inhibiting activator protein-1 and NF-kB pathways [72]. PPARg also plays roles in T cell differentiation and function [73].…”

Fish Oil Enhances T Cell Function and Tumor Infiltration and Is Correlated With a Cancer Prevention Effect in HER-2/neu But Not PyMT Transgenic Mice

“…cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase] (8). Furthermore, n-3 PUFAs activate peroxisome proliferator-activated receptor (PPAR) g, a member of the nuclear receptor superfamily and a transcription factor involved in lipid metabolism and innate and adaptive immunity (9).…”