IL-17 and CCR9 + α4β7 - Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren's Syndrome

Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populatio...

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Published in:Frontiers in immunology 2021-09, Vol.12, p.721453-721453
Main Authors: Hwang, Sun-Hee, Woo, Jin Seok, Moon, Jeonghyeon, Yang, SeungCheon, Park, Jin-Sil, Lee, JaeSeon, Choi, JeongWon, Lee, Kun Hee, Kwok, Seung-Ki, Park, Sung-Hwan, Cho, Mi-La
Format: Article
Language:English
Subjects:
aging
Animals
Biomarkers
Blood Glucose
Cell Death
Cell Self Renewal
Disease Models, Animal
Disease Susceptibility
gut-homing
Immunology
interleukin 17
Interleukin-17 - blood
Interleukin-17 - metabolism
Mice
Receptors, CCR - metabolism
Receptors, Lymphocyte Homing - metabolism
retinoic acid
Salivary Glands - immunology
Salivary Glands - metabolism
Salivary Glands - pathology
Sjogren's Syndrome - etiology
Sjogren's Syndrome - metabolism
Sjogren's Syndrome - pathology
Sjögren’s syndrome
Stem Cells - cytology
Stem Cells - metabolism
Th17 Cells - immunology
Th17 Cells - metabolism
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Summary:Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populations of T and B cells and SS disease severity. We detected increased populations of IL-17-producing T and B cells, which regulate inflammation, in the salivary glands of NOD/ShiLtJ mice. Inflammation-induced human submandibular gland cell death, determined based on p-MLKL and RIPK3 expression levels, was significantly increased by IL-17 treatment. Among IL-17-expressing cells in the salivary gland, peripheral blood, and spleen, the α4β7 (gut-homing integrin)-negative population was significantly increased in aged NOD/ShiLtJ mice. The α4β7-positive population markedly increased in the intestines of aged NOD/ShiLtJ mice following retinoic acid (RA) treatment. A significant increase in α4β7-negative IL-17-expressing cells in salivary glands may be involved in the onset and progression of SS. These results suggest the potential therapeutic utility of RA in SS treatment.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.721453