Clinical and experimental rheumatology · 2025
Dysregulated plasmacytoid dendritic cells in primary Sjögren's syndrome: normal functionality but decreased quantities.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Rongli, Jia Yimeng, Wu Xunyao, Wang Mu, Deng Chuiwen, Peng Yu, Zhao Lidan, Zhang Wen, Zhou Jiaxin, Li Mengtao, Zhao Yan, Zeng Xiaofeng, Fei Yunyun
Аннотация
OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterised by type I interferons (IFNs) signature, and plasmacytoid dendritic cell (pDC) is the primary producer of type I IFNs. However, the role of pDCs in the pathogenesis of pSS remains unclear. Our study aims to explore the dysregulation of pDCs in pSS, as well as the underlying mechanisms.
METHODS: In the present study, we included a total of 104 patients with pSS (64 were untreated and 40 were treated with hydroxychloroquine) and 64 healthy controls. We examined the frequency, activation markers, cytokines secretion, and infiltration into affected tissue of pDCs derived from pSS. Clinical correlation analyses and co-culture systems of pDCs and B cells were conducted to explore the pathogenesis of pDC reduction in pSS.
RESULTS: The frequency of pDC was significantly reduced in the peripheral blood of pSS. pDCs derived from pSS exhibited higher expression levels of Toll-like receptor 7 in the resting state. The IFN-α production by pDCs from pSS patients is similar to that of matched HC in vitro, regardless of whether the patients' IFN signature is negative or positive. Local invasion of pDCs into affected glands was detected but not common in pSS. In pSS patients, the proportion of circulating pDCs negatively correlated with serum IgG, IgA, and anti-SSA autoantibodies. pDCs promote proliferation, activation, differentiation, and antibody production of B cells. Conversely, excessive IgG promoted pDC apoptosis via neonatal Fc receptor (FcRn) and caused the decline of pDCs in pSS.
CONCLUSIONS: Our data enhances the understanding of pDC functionality in pSS and the mechanisms of their abnormal reduction in peripheral blood. We first report that excess IgG induced pDC apoptosis via FcRn and promoted the reduction of peripheral pDCs in patients with pSS.
METHODS: In the present study, we included a total of 104 patients with pSS (64 were untreated and 40 were treated with hydroxychloroquine) and 64 healthy controls. We examined the frequency, activation markers, cytokines secretion, and infiltration into affected tissue of pDCs derived from pSS. Clinical correlation analyses and co-culture systems of pDCs and B cells were conducted to explore the pathogenesis of pDC reduction in pSS.
RESULTS: The frequency of pDC was significantly reduced in the peripheral blood of pSS. pDCs derived from pSS exhibited higher expression levels of Toll-like receptor 7 in the resting state. The IFN-α production by pDCs from pSS patients is similar to that of matched HC in vitro, regardless of whether the patients' IFN signature is negative or positive. Local invasion of pDCs into affected glands was detected but not common in pSS. In pSS patients, the proportion of circulating pDCs negatively correlated with serum IgG, IgA, and anti-SSA autoantibodies. pDCs promote proliferation, activation, differentiation, and antibody production of B cells. Conversely, excessive IgG promoted pDC apoptosis via neonatal Fc receptor (FcRn) and caused the decline of pDCs in pSS.
CONCLUSIONS: Our data enhances the understanding of pDC functionality in pSS and the mechanisms of their abnormal reduction in peripheral blood. We first report that excess IgG induced pDC apoptosis via FcRn and promoted the reduction of peripheral pDCs in patients with pSS.