IP3Rs are sufficient for dendritic cell Ca2+ signaling in the absence of RyR1

Calcium (Ca(2+)) signaling plays a pivotal role in the function of dendritic cells (DC). The Type 1 ryanodine receptor (RyR), a major intracellular Ca(2+) channel, is highly expressed in immature DC. We therefore investigated whether RyR1 plays a role in DC development and function by studying properties of DC derived from wild-type (WT) and RyR1 null [knockout (KO)] mice. Fetal liver cells from WT and RyR1 KO mice retained full hematopoietic competence. Adoptive transfer of these cells into congenic hosts resulted in the generation of functionally equivalent DC populations. WT and RyR1 KO DC exhibited a similar capacity to mature in response to inflammatory and/or activation stimuli, to endocytose antigen, and to stimulate T cell proliferation. Moreover, the absence of RyR1 did not lead to de novo expression of RyR2 or RyR3. WT and RyR KO DC express all three isoforms of inositol 1,4,5-trisphosphate receptor (IP(3)R), although Type 3 IP(3)R gene transcripts are predominant. Further, IP(3)-mediated Ca(2+) transients proceed normally after inhibition of RyRs with dantrolene. Signaling via IP(3)R may therefore be sufficient to drive essential DC Ca(2+) signaling processes in the absence of RyR expression or function.