Potential role of store-operated Ca2Â + entry in Th2 response induced by histamine in human monocyte-derived dendritic cells

Store-operated calcium entry (SOCE) is the main Ca2 + influx pathway of dendritic cells (DCs). DCs primed with histamine facilitate Th2 immune response via different types of histamine receptors. Histamine induces DCs to release Ca2 + from internal store. Therefore, we wonder that whether histamine could activate SOCE in DCs through its receptors, and what's the functional relevance of the Ca2 + influx through SOCE induced by histamine in Th2 response. We certificate that histamine induced a transient Ca2 + release followed by pronounced Ca2 + influx after re-addition of external Ca2 + which could be inhibited by SOCE blockers SKF-96365 and BTP-2. Moreover, the percentages of DCs that showed an obvious Ca2 + release response to histamine were decreased in the presence of histamine 1 (H1) receptor antagonist pyridylethylamine (Pyr) or histamine 4 (H4) receptor antagonist JNJ7777120 (JNJ). Histamine up-regulated the mRNA expression of STIM1 in DCs, one of the two major proteins of SOCE channel. SOCE blocker BTP-2 and histamine receptor antagonists JNJ and Pyr inhibited the increase of CD86 induced by histamine on DCs. Histamine increased the level of IL-10 and decreased the level of IL-12p70 secreted by DCs. SOC blockers SKF and BTP-2 inhibited the level of both IL-10 and IL-12p70 secreted by DCs. Pretreatment of SOC blockers and H1, H4 receptor antagonists with DCs inhibited the Th2 polarization of T helper cells induced by histamine in mixed lymphocyte responses (MLR). We demonstrated that SOCE was involved in histamine-induced maturation and Th2 response of DCs which was through histamine 1 and 4 receptor.

► Store-operated Ca2 + entry (SOCE) participated in the maturation of human dendritic cells (DCs). ► Up-regulation of STIM1 mRNA may contribute to the maturation of DCs induced by histamine. ► We confirmed that histamine promoted the Th2 response via SOCE in DCs. ► Both histamine 1 and 4 receptors took part in the SOCE induced by histamine in DCs.