Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes.
BACKGROUND
Vitamin A (VA) deficiency induces a type 1 cytokine response and exogenously provided retinoids can induce a type 2 cytokine response both in vitro and in vivo. The precise mechanism(s) involved in this phenotypic switch are inconsistent and have been poorly characterized in humans. In an effort to determine if retinoids are capable of inducing Th2 cytokine responses in human T cell cultures, we stimulated human PBMCs with immobilized anti-CD3 mAb in the presence or absence of all-trans retinoic acid (ATRA) or 9-cis-RA.


RESULTS
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-gamma, IL-2, IL-12p70 and TNF-alpha 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.


CONCLUSIONS
These data provide strong evidence for multiple inductive roles for retinoids in the development of human type-2 cytokine responses.
Dawson
Harry D
HD
Nutrient Requirement and Functions Laboratory, United States Department of Agriculture, Beltsville, MD, USA. harry.dawson@ars.usda.gov <harry.dawson@ars.usda.gov>
Collins
Gary
G
Pyle
Robert
R
Key
Michael
M
Weeraratna
Ashani
A
Deep-Dixit
Vishwa
V
Nadal
Celeste N
CN
Taub
Dennis D
DD
D000328:Adult; D000077556:Alitretinoin; D018106:CD28 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*
D018106:CD28 Antigens; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D000077556:Alitretinoin; D014212:Tretinoin