Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease affecting mainly women of childbearing age. This disease is characterized by the presence in patient blood of autoreactive antibodies mainly raised against nuclear antigens. These autoantibodies will form circulating immune complexes (CIC) which will deposit in targeted organs such as skin, joints, connective tissues and kidney, leading to the development of a chronic inflammation. Kidney affection in SLE, known as lupus nephritis, can lead to kidney damage and failure. We previously showed that basophils, cells known to contribute to allergy, amplify the synthesis of autoantibodies by accumulating in secondary lymphoid organs. Here, we show a role for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2 receptors (PTGDR) on blood basophils and increased concentration of PGD2 metabolite in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDRs axis as a ready-to-use therapeutic modality in SLE.

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Nature Reviews in Nephrology, May 2018 Vol 14 n°5,