科研之友
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摘要
Maintaining an appropriate balance between subsets of CD4(+) helper T cells and Tregulatory cells (Tregs) is a critical process in immune homeostasis and a protective mechanism against autoimmunity and inflammation. To identify the role of vitamin A-related compounds, we investigated the regulation of interleukin (IL)-17-producing helper T cells (Th17 cells) and Tregs treated with all-trans-retinal (retinal). CD4(+)T cells or total cells from the spleens of C57BL/6 mice were stimulated under Treg-polarizing (anti-CD3/CD28 and TGF-beta) or Th17-polarizing (anti-CD3/CD28, TGF-beta, and IL-6) conditions in the presence or absence of retinal. To analyze their suppressive abilities, retinal-induced Tregs or TGF-beta-induced Tregs were co-cultured with responder T cells. Collagen-induced arthritis (CIA) was established in interferon (IFN)-gamma knockout mice. On day 13, retinal-induced Tregs were adoptively transferred to mice with established CIA after second immunizations. Compared with TGF-beta-induced Treg cells, retinal-induced Tregs showed increased Foxp3 expression and mediated stronger suppressive activity. Under Th17-polarizing conditions, retinal inhibited the production of IL-17 and increased the expression of Foxp3. Retinal-induced Tregs showed therapeutic effects in IFN-gamma knockout CIA mice. Thus, we demonstrated that retinal reciprocally regulates Foxp(3+) Tregs and Th17 cells. These findings suggest that retinal, a vitamin A metabolite, can regulate the balance between pro-and anti-inflammatory immunity. A better understanding of the manipulation of Foxp3 and Tregs may enable the application of this tremendous therapeutic potential in various autoimmune diseases.
- 出版日期2012-9
- 单位河北医科大学
