Deficiency of RIPK3 (receptor-interacting protein kinase 3) in antigen-presenting cells dampens the pro-inflammatory T cell response following antigen presentation

Abstract STUDY OBJECTIVE: We have previously shown that RIPK3 (receptor-interacting protein kinase 3)-deficient mice are protected from the development of an induced murine model of systemic lupus erythematosus (SLE). The development of SLE autoantibodies in this model is associated with the generation of an antigen-specific T cell response. We hypothesize that RIPK3-deficient antigen-presenting cells (APCs) are impaired in generation of a robust T cell response, thereby impacting induction of SLE in our murine model. METHODS: We performed a complete cellular immunophenotyping on mice deficient in RIPK3, compared with wild type C57BL/6 mice. We also assessed the function of RIPK3-deficient APCs in an in vitro antigen presentation assay using ovalbumin (OVA) and OVA-specific OT-II T cells. RESULTS: No major differences in immune cell composition and phenotype were identified between naïve RIPK3-deficient and WT mice. However, RIPK3-deficient bone marrow-derived dendritic cells (BMDCs) were found to produce lower levels of pro-inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) following lipopolysaccharide (LPS) stimulation. Moreover, presentation of OVA by RIPK3-deficient BMDCs resulted in a lower proportion of interferon (IFN)-γ producing OT-II T cells, compared to antigen presentation by WT BMDCs. In contrast, T cell proliferation was similar whether antigen was presented by RIPK3-deficient or WT BMDCs. CONCLUSION: Our results suggest that RIPK3 deficiency in APCs impacts antigen presentation to T cells, identifying a possible mechanism by which RIPK3-deficient mice are protected from induction of SLE.