ITK deficiency protects against autoimmune pulmonary hemorrhage by promoting Amphiregulin producing regulatory T cells
Hossain, M. S.; Mobeen, A.; Topkaya, I. H.; Xiong, H.; Trevail, R.; Chen, L.; Suo, L.; Karimi, M. · immunology · 2026-09-04 · 原文
DOI：10.64898/2026.05.01.722312作者：8 位
Pulmonary hemorrhage (PH) is a life-threatening manifestation of systemic autoimmunity caused by immune-mediated disruption of the alveolar capillary barrier. Despite high mortality, the molecular checkpoints that shift destructive inflammation toward protective immune regulation remain poorly defined. Here, using the pristane-induced PH model, we identify interleukin-2-inducible T cell kinase (ITK) as a critical regulator of autoimmune lung injury. ITK deficiency (ITK-/- ) conferred near-complete protection from PH and associated multiorgan injury, accompanied by reduced proinflammatory monocytes and neutrophils and increased Foxp3 regulatory T cells (Tregs). Adoptive transfer of ITK-/-; Tregs protected wild-type recipients from PH and suppressed systemic proinflammatory cytokines, identifying Tregs as key mediators of tissue protection. Mechanistically, lung ITK-/- ; Tregs exhibited increased amphiregulin, a mediator of tissue repair. Transcriptomic profiling further showed that ITK loss reprogrammed Tregs toward a metabolically and functionally enhanced state, with enrichment of oxidative phosphorylation, mTORC1 and STAT5 signaling, and tissue-repair programs. These findings est
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1. 人话版
Pulmonary hemorrhage (PH) is a life-threatening manifestation of systemic autoimmunity caused by immune-mediated disruption of the alveolar capillary barrier.
Despite high mortality, the molecular checkpoints that shift destructive inflammation toward protective immune regulation remain poorly defined.
2. 领域脉络
本文类目：immunology，属于其所在研究脉络的最新进展。
3. 机制拆解
Adoptive transfer of ITK-/-; Tregs protected wild-type recipients from PH and suppressed systemic proinflammatory cytokines, identifying Tregs as key mediators of tissue protection.
4. 证据与数字
Here, using the pristane-induced PH model, we identify interleukin-2-inducible T cell kinase (ITK) as a critical regulator of autoimmune lung injury.
ITK deficiency (ITK-/- ) conferred near-complete protection from PH and associated multiorgan injury, accompanied by reduced proinflammatory monocytes and neutrophils and increased Foxp3 regulatory T cells (Tregs).
Transcriptomic profiling further showed that ITK loss reprogrammed Tregs toward a metabolically and functionally enhanced state, with enrichment of oxidative phosphorylation, mTORC1 and STAT5 signaling, and tissue-repair programs.
5. 反例与边界
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6. 跨领域连接与意外收获
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8. 术语表
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