CUTTING EDGE - INDUCTION OF IL-10 SYNTHESIS BY HUMAN KERATINOCYTES THROUGH CD23 LIGATION - A CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-DEPENDENTMECHANISM

Ligation of the low affinity receptor for IgE, CD23/Fc epsilon RII. in human keratinocytes (HK) and monocytes induces the synthesis of proin flammatory cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric oxide pathways. Moreover, CD23 ligation induces IL -10 production in human monocytes. Since synthesis of IL-10 by HK is s till a matter of debate, we investigate whether keratinocytes could pr oduce IL-10 upon CD23 stimulation. Here, our data show that CD23 ligat ion induces significant IL-10 synthesis in HK, a phenomenon inhibited by cAMP antagonists, but not by inhibitors of the nitric oxide pathway . Accordingly, cAMP agonist induced significant IL-10 synthesis by HK, while nitric oxide-releasing chemical did not. Treatment of HK with a nti-IL-10 mAb potentiated their CD23-mediated TNF-alpha synthesis. The se data indicate that engagement of surface CD23 on human keratinocyte s induces the synthesis of IL-10, which, in turn, downregulates their proinflammatory response.