In Vivo Response of γδ T Cells and Macrophages to Non-Bilayer Phospholipid Arrangements in a Lupus-like Mouse Model.

Anti-lipid autoantibodies are produced in systemic lupus erythematosus (SLE). These antibodies are associated with clinical manifestations of the disease, such as thrombosis, cardiovascular events, and neurological disorders. However, the cellular and molecular mechanisms that lead to the production of these antibodies are not well known. We developed a mouse model of lupus by administering liposomes bearing non-bilayer phospholipid arrangements (NPA) stabilized by chlorpromazine. These mice produce anti-NPA antibodies that trigger a lupus-like disease. In previous studies, we demonstrated that these antibodies are primarily produced by germinal centers and that NK1.1 CD4 T cells provide help to B cells, enabling them to produce these IgG antibodies. However, additional immune cells may contribute to the production of these antibodies. Therefore, in this work, we analyzed the in vivo responses of γδ T cells and macrophages in this mouse model. We found that γδ T cells from mice that produce anti-NPA antibodies produce IFNγ and IL-17, which can contribute to B cell class switching and production of anti-NPA IgG antibodies via germinal centers. Additionally, we found that macrophages are polarized into a proinflammatory M1 phenotype and produce IL-6 that can exacerbate inflammation and potentially lead to autoimmunity.