CD4 T cell-secreted IFN-γ in Sjögren's syndrome induces salivary gland epithelial cell ferroptosis

Zhou, Jiannan; Pathak, Janak L.; Cao, Tingting; Chen, Bo; Wei, Wei; Hu, Shilin; Mao, Tianjiao; Wu, Xiaodan; Watanabe, Nobumoto; Li, Xiaomeng; Li, Jiang

doi:10.1016/j.bbadis.2024.167121

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2024

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Cited by 5 publications

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Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Liu,

Mao,

Liu

et al. 2024

International Immunopharmacology

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Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Liu,

Mao,

Liu

et al. 2024

International Immunopharmacology

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Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome

Huang,

Tang,

Zhang

et al. 2024

Journal of Translational Autoimmunity

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IFN-γ–producing T _H 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease

Wang,

Li,

McDermott

et al. 2024

Sci. Transl. Med.

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Sjögren’s disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T reg ) cells occur in several autoimmune diseases, but their role in SjD is ambiguous. We had previously shown that the function and development of T reg cells depend on store-operated Ca 2+ entry (SOCE), which is mediated by ORAI1 Ca 2+ channels and stromal interaction protein 1 (STIM1) and STIM2. Here, we show that mice with a Foxp3 + T reg cell–specific deletion of Stim1 and Stim2 develop a phenotype that fulfills all classification criteria of human SjD. Mutant mice have salivary and lacrimal gland inflammation characterized by strong lymphocyte infiltration and transcriptional signatures dominated by T helper 1 (T H 1) and interferon (IFN) signaling. CD4 + T cells from mutant mice are sufficient to induce SjD-like disease in an IFN-γ–dependent manner. Inhibition of IFN signaling with the JAK1/2 inhibitor baricitinib alleviated CD4 + T cell–induced SjD in mice. These findings are consistent with the transcriptional profiles of CD4 + T cells from patients with SjD, which indicate enhanced T H 1 but reduced memory T reg cell function. Together, our study provides evidence for a critical role of dysfunctional T reg cells and IFN-γ–producing T H 1 cells in the pathogenesis of SjD.

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CD4 T cell-secreted IFN-γ in Sjögren's syndrome induces salivary gland epithelial cell ferroptosis

Cited by 5 publications

References 59 publications

Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome

IFN-γ–producing T _H 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease

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CD4 T cell-secreted IFN-γ in Sjögren's syndrome induces salivary gland epithelial cell ferroptosis

Cited by 5 publications

References 59 publications

Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Apigenin alleviates Sjögren’s syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis

Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome

IFN-γ–producing T H 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease

Contact Info

Product

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About

IFN-γ–producing T _H 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease