Thursday Seminar: John Tchen

15/09/2022

Speaker

John Tchen

Description

« Mécanismes de l’amplification de la pathogénie lupique dépendante des basophiles : La relation basophile – TFH » Resume: Systemic Lupus Erythematosus (SLE) is a rare autoimmune disease of multifactorial etiology mainly affecting women of child-bearing age. SLE can affect multiple organs such as skin, joints, central nervous system and/or kidneys. Lupus nephritis (LN) affects ~35% of SLE patients and can lead to end stage renal disease in around 20% of them. Identification of specific and efficacious treatments is of primary interest to optimize SLE patient care since, currently, flares of the disease are contained with high doses of corticosteroids and immunosuppressive drugs. SLE is characterized by the presence in patients’ serum of autoreactive antibodies raised against nuclear antigens (double stranded (ds) DNA, ribonucleoproteins (RNP)…). Once aggregated to their autoantigen and complement factors, they form circulating immune complexes (CIC) that deposit in target organs where they induce inflammatory lesions. In parallel, CIC activate innate immune cells that will promote and amplify, by diverse mechanisms, autoantibody production. T follicular helper cells (TFH) are the main subset of CD4+ T cells providing help to B cells to promote their differentiation into antibody-secreting cells (ASC). Their involvement in lupus pathogenesis is well established since their number and their ability to provide help to B cells are known to be increased during the course of the disease. Key contribution of basophils and IgE in SLE pathogenesis have been demonstrated in lupus-like mouse models and in SLE patients. By accumulating in secondary lymphoid organs (SLO), basophils amplify autoantibody production by supporting the number and the differentiation of autoreactive plasma cells. However, mechanisms by which this basophil- dependent autoantibody production amplification occurs in SLO remained to be defined. This work aimed at describing and deciphering these mechanisms inside SLO and establish a functional relationship between basophils and TFH in lupus pathophysiology both in lupus-like mouse models and in SLE patient samples and provides new insights in lupus disease amplification mechanisms and some new putative therapeutic targets. The latter may lead to prevent basophil – TFH interaction and thus limit the number and/or the extent of disease flares in SLE patients.
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