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Published online before print July 14, 2006

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(Journal of Leukocyte Biology. 2006;80:651-658.)
© 2006 by Society for Leukocyte Biology

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

Meaghan Stolk^*, Matilde Leon-Ponte^*, Mia Merrill^*, Gerard P. Ahern^,1 and Peta J. O’Connell^*,2

^* Robarts Research Institute, London, Ontario, Canada; and
Georgetown University, Washington, DC

¹ Correspondence: Georgetown University, MedDent SW401, 3900 Reservoir Rd., Washington, DC 20007. E-mail: gpa3{at}georgetown.edu

Calcium (Ca²⁺) signaling plays a pivotal role in the function of dendritic cells (DC). The Type 1 ryanodine receptor (RyR), a major intracellular Ca²⁺ 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 (IP₃R), although Type 3 IP₃R gene transcripts are predominant. Further, IP₃-mediated Ca²⁺ transients proceed normally after inhibition of RyRs with dantrolene. Signaling via IP₃R may therefore be sufficient to drive essential DC Ca²⁺ signaling processes in the absence of RyR expression or function.

Key Words: calcium • ryanodine receptors • leukocytes • immune function

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