STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus-like Autoimmune- and Foreign Antigen-Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses.

Autor:	Fike AJ; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033., Chodisetti SB; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033., Bricker KN; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033., Choi NM; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033., Chroneos ZC; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033.; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033.; Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, PA 17033; and., Kaplan MH; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202., Rahman ZSM; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033; zrahman@pennstatehealth.psu.edu.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2021 Jan 14; Vol. 5 (1), pp. 2-15. Date of Electronic Publication: 2021 Jan 14.
DOI:	10.4049/immunohorizons.2000111
Abstrakt:	Genome-wide association studies identified variants in the transcription factor STAT4 gene and several other genes in the STAT4 signaling pathway, such as IL12A , IL12B , JAK2 , and TYK2 , which are associated with an increased risk of developing systemic lupus erythematosus (SLE) and other autoimmune diseases. Consistent with the genome-wide association studies data, STAT4 was shown to play an important role in autoimmune responses and autoimmunity development in SLE mouse models. Despite such important role for STAT4 in SLE development in mice and humans, little is known whether and how STAT4 may regulate extrafollicular Ab-forming cell (AFC) and follicular germinal center (GC) responses, two major pathways of autoreactive B cell development and autoantibody production. To our surprise, we found STAT4 to be largely dispensable for promoting autoimmune AFC and GC responses in various autoimmune- and SLE-prone mouse models, which strongly correlated with autoantibody production, and immune complex deposition and immune cell infiltration in the kidney. We further observed that STAT4 deficiency had no effects on AFC, GC, and Ag-specific Ab responses during protein Ag immunization or influenza virus infection. Additionally, CD4 + effector and follicular Th cell responses in autoimmune- and SLE-prone mice and protein Ag-immunized and influenza virus-infected mice were intact in the absence of STAT4. Together, our data demonstrate a largely dispensable role for STAT4 in AFC, GC, and Ab responses in SLE mouse models and in certain foreign Ag-driven responses. (Copyright © 2021 The Authors.)
Databáze:	MEDLINE
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