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 intra- cellular Ca 2 channel, is highly expressed in im- mature 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 re- tained 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 inflam- matory and/or activation stimuli, to endocytose an- tigen, and to stimulate T cell proliferation. More- over, 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 (IP3R), although Type 3 IP3R gene transcripts are predominant. Further, IP3-mediated Ca 2 transients proceed normally af- ter inhibition of RyRs with dantrolene. Signaling via IP3R may therefore be sufficient to drive essen- tial DC Ca 2 signaling processes in the absence of RyR expression or function. J. Leukoc. Biol. 80: 651-658; 2006.