Retinoic Acid Stimulates the Cell Cycle Machinery in Normal T Cells: Involvement of Retinoic Acid Receptor-Mediated IL-2 Secretion

• DOI: 10.4049/jimmunol.169.10.5555
• Publication Date: 2014-04-21T00:04:08Z
• Authors: Aase Ertesvag; Nikolai Engedal; Soheil Naderi; Heidi Kiil Blomhoff
• Keywords: Retinoblastoma protein

Abstract The mechanisms whereby vitamin A stimulates the immune system are poorly understood. In current study, we attempted to elucidate potential of action all-trans retinoic acid (atRA) on proliferation human T lymphocytes. We found that physiological levels atRA potently augmented cell when added in combination with common cell-stimulating agents. This was reflected a time- and concentration-dependent stimulation cycle machinery. presence led elevated cyclin D3, -E, -A, decreased p27Kip1, increased activity cyclin-dependent kinase 2, enhanced phosphorylation retinoblastoma protein (pRB). atRA-mediated changes machinery were late events, appearing after 20 h stimulation, indicating effects indirect. did not alter expression high-affinity IL-2R. However, level IL-2 secreted by cells strongly atRA. rIL-2 able substitute for DNA synthesis, blocking IL-2R markedly inhibited atRA-induced pRB phosphorylation. receptor (RAR)-selective agonist 9-cis-RA had same potency as secretion, whereas retinoid X receptor-selective only marginal effects. Furthermore, RAR-selective antagonist completely suppressed induced Taken together, these results suggest normal increasing secretion through involving RARs.