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 populations of...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.721453/full |
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| author | Sun-Hee Hwang Jin Seok Woo Jeonghyeon Moon SeungCheon Yang Jin-Sil Park JaeSeon Lee JeongWon Choi Kun Hee Lee Kun Hee Lee Seung-Ki Kwok Seung-Ki Kwok Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho |
| author_facet | Sun-Hee Hwang Jin Seok Woo Jeonghyeon Moon SeungCheon Yang Jin-Sil Park JaeSeon Lee JeongWon Choi Kun Hee Lee Kun Hee Lee Seung-Ki Kwok Seung-Ki Kwok Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho |
| author_sort | Sun-Hee Hwang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T08:19:58Z |
| format | Article |
| id | doaj.art-446ce04b01fb4a4189e807785a8a6da2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T08:19:58Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-446ce04b01fb4a4189e807785a8a6da22022-12-21T22:38:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.721453721453IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s SyndromeSun-Hee Hwang0Jin Seok Woo1Jeonghyeon Moon2SeungCheon Yang3Jin-Sil Park4JaeSeon Lee5JeongWon Choi6Kun Hee Lee7Kun Hee Lee8Seung-Ki Kwok9Seung-Ki Kwok10Sung-Hwan Park11Sung-Hwan Park12Mi-La Cho13Mi-La Cho14The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDivison of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDivison of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, South KoreaPrevious 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.721453/fullSjögren’s syndromeaginginterleukin 17gut-homingretinoic acid |
| spellingShingle | Sun-Hee Hwang Jin Seok Woo Jeonghyeon Moon SeungCheon Yang Jin-Sil Park JaeSeon Lee JeongWon Choi Kun Hee Lee Kun Hee Lee Seung-Ki Kwok Seung-Ki Kwok Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome Frontiers in Immunology Sjögren’s syndrome aging interleukin 17 gut-homing retinoic acid |
| title | IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome |
| title_full | IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome |
| title_fullStr | IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome |
| title_full_unstemmed | IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome |
| title_short | IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome |
| title_sort | il 17 and ccr9 α4β7 th17 cells promote salivary gland inflammation dysfunction and cell death in sjogren s syndrome |
| topic | Sjögren’s syndrome aging interleukin 17 gut-homing retinoic acid |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.721453/full |
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