Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Hwang SH

PROVIDER: S-EPMC8440850 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Hwang Sun-Hee SH Woo Jin Seok JS Moon Jeonghyeon J Yang SeungCheon S Park Jin-Sil JS Lee JaeSeon J Choi JeongWon J Lee Kun Hee KH Kwok Seung-Ki SK Park Sung-Hwan SH Cho Mi-La ML

Frontiers in immunology 20210901

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 ...[more]

PMID: 34539657

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Project description:ObjectiveA major characteristic of the autoimmune disease primary Sjögren's syndrome (SS) is salivary gland (SG) hypofunction. The inability of resident SG stem cells (SGSCs) to maintain homeostasis and saliva production has never been explained and limits our comprehension of mechanisms underlying primary SS. The present study was undertaken to investigate the role of salivary gland stem cells in hyposalivation in primary SS.MethodsSGSCs were isolated from parotid biopsy samples from controls and patients classified as having primary SS or incomplete primary SS, according to the American College of Rheumatology/European League Against Rheumatism criteria. Self-renewal and differentiation assays were used to determine SGSC regenerative potential, RNA was extracted for sequencing analysis, single telomere length analysis was conducted to determine telomere length, and frozen tissue samples were used for immunohistochemical analysis.ResultsSGSCs isolated from primary SS parotid gland biopsy samples were regeneratively inferior to healthy control specimens. We demonstrated that SGSCs from samples from patients with primary SS are not only lower in number and less able to differentiate, but are likely to be senescent, as revealed by telomere length analysis, RNA sequencing, and immunostaining. We further found that SGSCs exposed to primary SS-associated proinflammatory cytokines we induced to proliferate, express senescence-associated genes, and subsequently differentiate into intercalated duct cells. We also localized p16+ senescent cells to the intercalated ducts in primary SS SG tissue, suggesting a block in SGSC differentiation into acinar cells.ConclusionThis study represents the first characterization of SGSCs in primary SS, and also the first demonstration of a linkage between an autoimmune disease and a parenchymal premature-aging phenotype. The knowledge garnered in this study indicates that disease-modifying antirheumatic drugs used to treat primary SS are not likely to restore saliva production, and should be supplemented with fresh SGSCs to recover saliva production.

Project description:BackgroundSince gamma delta (γδ) T cells are involved in various autoimmune diseases, we aimed to verify whether γδ T cells participate in the pathogenesis of Sjögren's syndrome (SS) and related pulmonary inflammation, and also aimed to evaluate the effects of umbilical cord mesenchymal stem cells (MSCs) on SS-related pulmonary inflammation and the γδ T cells.MethodsThe saliva flow rates of female non-obese diabetic (NOD/Ltj) mice were measured. Histopathologic analysis was performed in salivary glands (SG) and lung tissues. The levels of γδ T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified γδ T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice.ResultsThe results showed lymphocytic infiltration in SG and lacrimal glands (LG), and reduction of saliva flow rates in 8-week NOD/Ltj mice. The levels of γδ T cells decreased in peripheral blood, but increased in the lung of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of Vγ4+ T cells and Vγ4+ IL-17A+ T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of γδ T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of Vγ4+ T cells and Vγ4+ IL-17A+ T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that γδ T cells and Vγ4+ T cells contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing Vγ4+ IL-17A+ T cells.ConclusionsPeripheral Vγ4+ T cells infiltrate into the lung in SS mice, and aggravate the symptoms of SS and SS-related pulmonary inflammation by secreting IL-17A. Meanwhile, lymphocyte infiltration could be reversed by MSC transplantation, which indicates the potential of MSCs in the treatment of SS and SS-related pulmonary inflammation patients.

Dataset Information

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

Publications

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

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Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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