%0 Journal Article
%T Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes
%A Harry D Dawson
%A Gary Collins
%A Robert Pyle
%A Michael Key
%A Ashani Weeraratna
%A Vishwa Deep-Dixit
%A Celeste N Nadal
%A Dennis D Taub
%J BMC Immunology
%D 2006
%I BioMed Central
%R 10.1186/1471-2172-7-27
%X Stimulation of human PBMCs and purified T cells with ATRA and 9-cis-RA increased mRNA and protein levels of IL-4, IL-5, and IL-13 and decreased levels of IFN-¦Ã, IL-2, IL-12p70 and TNF-¦Á upon activation with anti-CD3 and/or anti-CD28 mAbs. These effects were dose-dependent and evident as early as 12 hr post stimulation. Real time RT-PCR analysis revealed a dampened expression of the Th1-associated gene, T-bet, and a time-dependent increase in the mRNA for the Th2-associated genes, GATA-3, c-MAF and STAT6, upon treatment with ATRA. Besides Th1 and Th2 cytokines, a number of additional proinflammatory and regulatory cytokines including several chemokines were also differentially regulated by ATRA treatment.These data provide strong evidence for multiple inductive roles for retinoids in the development of human type-2 cytokine responses.An uncommitted precursor T helper (pTh) cell can be induced to differentiate into at least two distinct subsets of effector cells, T helper type 1 (Th1) and T helper type 2 (Th2) cells [1,2]. Th1 cells secrete IFN-¦Ã, TNF-¦Á, and TNF-¦Â and are important for the development of delayed type hypersensitivity (DTH) reactions and protective responses to intracellular pathogens [1,2]. These cells also contribute to the pathology of autoimmune disease and graft rejection. Th2 cells express and secrete IL-4, IL-5, and/or IL-13 and are essential for the development of humoral and allergic reactions [1,2]. During T cell activation, the relative cytokine milieu within the local microenvironment is a major determinant of the direction of pTh cell differentiation. Cytokines such as IL-12 and to a lesser extent IFN-¦Ã directly induce pTh cell differentiation into type 1 cells [1]. In contrast, IL-4 stimulates pTh cell differentiation into type 2 cells even in the presence of moderate levels of IL-12 and IFN-¦Ã [2]. In addition to IFN-¦Ã, IL-12 and IL-4, recent evidence also suggests an important role for cytokines such as IFN-(, IL-1¦Á/¦Â, IL-15, and IL-18 i
%U http://www.biomedcentral.com/1471-2172/7/27