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

Adam J. Fike, Sathi Babu Chodisetti, Kristen N. Bricker, Nicholas M. Choi, Zissis C. Chroneos, Mark H. Kaplan, Ziaur Rahman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2-15
Number of pages14
JournalImmunoHorizons
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2021

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy

Fingerprint

Dive into the research topics of 'STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus–like Autoimmune- And Foreign Antigen–Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses'. Together they form a unique fingerprint.

Cite this