ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1506124
RIPK3 impacts antibody generation in an induced model of murine lupus through mechanisms other than necroptosis and antigen presentation
Provisionally accepted
- 1McGill University, Montreal, Canada
- 2Research Institute, McGill University Health Center, Montreal, Quebec, Canada
- 3University of Illinois Chicago, Chicago, Illinois, United States
- 4Jesse Brown VA Medical Center, United States Department of Veterans Affairs, Chicago, Illinois, United States
- 5Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
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Receptor-interacting protein kinase 3 (RIPK3) is a protein involved in cell death and inflammatory processes. The most recognized function of RIPK3 is the induction of necroptosis, an inflammatory type of cell death that is dependent on RIPK3 kinase activity. Deficiency in RIPK3-dependent pathways has been associated with protection from various inflammatory and autoimmune conditions. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the generation of autoantibodies to multiple intracellular antigens leading to multi-organ pathology. Little is known about the involvement of RIPK3-dependent pathways in SLE. We have previously shown that autoantibody generation in an induced model of murine lupus is impaired in RIPK3deficient mice. The current study aimed to identify the RIPK3-dependent mechanisms that contribute to autoantibody generation in this induced model of murine lupus. Generation of autoantibodies to SLE antigens following immunization with β2GPI and LPS was found to be dependent on RIPK3 activity, but independent of MLKL (i.e., RIPK3-dependent necroptosis).Bone marrow chimeric experiments revealed that RIPK3 mediates autoantibody generation through both immune and non-immune compartments. RIPK3 deficiency within antigen presenting cells did not impact T cell activation in vitro. Moreover, early and late T cell activation ex vivo was not impaired in RIPK3-deficient mice following induction of murine lupus. These results suggest that RIPK3 contributes to autoantibody generation in our induced model of murine lupus through an interplay of pathways that appear to be independent of necroptosis and antigen presentation.
Keywords: systemic lupus erythematosus, Receptor-interacting protein kinase 3 (RIPK3), Antigen Presentation, Autoantibodies, murine model, Cell Death
Received: 04 Oct 2024; Accepted: 30 Jul 2025.
Copyright: © 2025 Pilon, Lonina, Levine, Lesage and Rauch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joyce Rauch, McGill University, Montreal, Canada
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