IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease. Clin Immunol 2024 Jul;264:110260
Date
05/25/2024Pubmed ID
38788885Pubmed Central ID
PMC11203157DOI
10.1016/j.clim.2024.110260Scopus ID
2-s2.0-85193848203 (requires institutional sign-in at Scopus site)Abstract
Sjögren's disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39hi exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.
Author List
Debreceni IL, Barr JY, Upton EM, Chen YG, Lieberman SMAuthor
Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApyrase
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Disease Models, Animal
Female
Inducible T-Cell Co-Stimulator Protein
Interleukin-27
Interleukins
Lacrimal Apparatus
Mice
Mice, Inbred NOD
Programmed Cell Death 1 Receptor
Receptors, Interleukin
Signal Transduction
Sjogren's Syndrome
