Studying the Role for CD4+ T Cell Subsets in Human Lupus
Annual rept. 1 Jul 2012-30 Jun 2013
YALE UNIV NEW HAVEN CT
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We have investigated whether and how autoimmune complex AIC in SLE lupus can induce T helper Th cell polarizing cytokines including IL-27 and IL-1 , leading to enhanced Th cell responses. We have measured IL-27 gene and protein expression by healthy human monocytes g Istimulated with autoimmune complex containing anti-dsDNA and snRNP antibodies using qPCR and ELISA, respectively. However, levels of IL-27 produced from the stimulated monocytes were relatively low compared to those of the pro-inflammatory cytokine IL-1 . IL-1 promotes of the development of Th17 cells that is increased in lupus patients. Increased IL-1 expression was found in the target tissues of lupus patients although the mechanism for these findings is unknown. It is conceivable that a combination of IL-27 and IL-1 can promote the development of Th17 cells with the capacity to produce IL-10, a notion in accordance with our original hypothesis. We have reported that AIC containing dsDNA and U1-snRNP activate human monocytes dependently of anti-dsDNA and U1-snRNP antibodies, respectively, leading to the production of cytokines including IL-1 . This phenomenon was dependent on the activation of Toll-like receptor and NLRP3 inflammasome pathways. We also found that IL-27 can suppress IL-17 production in human CD4 T cells and that such suppression is enhanced in patients with SLE. This finding suggests a potential therapeutic implication of exogenous IL-27 in patients with SLE.
- Medicine and Medical Research