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Nat Commun. 2018 Feb 20;9(1):725. doi: 10.1038/s41467-018-03129-8.

Prostaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs.

Author information

1
Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Sorbonne Paris Cité, Faculté de Médecine site Bichat, Laboratoire d'Excellence Inflamex, DHU FIRE, Université Paris Diderot, 16 rue Henri Huchard, 75018, Paris, France.
2
INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Institut Imagine, 24 boulevard du Montparnasse, 75015, Paris, France.
3
Department of Nephrology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine site Bichat, DHU FIRE, Université Paris Diderot, 46 rue Henri Huchard, 75018, Paris, France.
4
Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine site Bichat, DHU FIRE, Université Paris Diderot, 46 rue Henri Huchard, 75018, Paris, France.
5
Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.
6
Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Sorbonne Paris Cité, Faculté de Médecine site Bichat, Laboratoire d'Excellence Inflamex, DHU FIRE, Université Paris Diderot, 16 rue Henri Huchard, 75018, Paris, France. nicolas.charles@inserm.fr.

Abstract

In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils 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 metabolites 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/PTGDR axis as a ready-to-use therapeutic modality in SLE.

PMID:
29463843
PMCID:
PMC5820278
DOI:
10.1038/s41467-018-03129-8
[Indexed for MEDLINE]
Free PMC Article

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