In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 7, No. 72 ( 2022-06-24)
Abstract:
Human FOXP3 encodes two major isoforms regulated by alternative splicing: a full-length isoform and an isoform lacking exon 2 (FOXP3 ΔE2). How these isoforms differ in regulating T reg function is not well understood. Du et al. generated a mouse model in which T regs express only FOXP3 ΔE2 and identified that these mice developed systemic autoimmunity featuring anti-dsDNA autoantibodies and immune complex glomerulonephritis, caused by exacerbated T FH and germinal center responses. Expression of the FOXP3 ΔE2 isoform resulted in T reg instability, increased expression of inflammatory cytokines, and down-regulation of positive regulators of Foxp3. Furthermore, human patients who expressed only the FOXP3 ΔE2 isoform developed immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. These results identify FOXP3 exon 2 as a critical regulator of T reg function.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abo5407
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
Permalink