β-Catenin Stabilization Protects Against Alveolar Hemorrhage Through Amphiregulin and BATF-Mediated Regulatory T Cells

Fiona Mason; Hui Xiong; Ali Mobeen; Md Saddam Hossain; Sara Mahmudlu; Rosanne Trevail; Mikyal Mobeen; Li Chen; Sunny Lee; Tuncay Delibasi; Jyoti Misra Sen; Mobin Karimi

doi:10.1172/jci.insight.201552

β-Catenin Stabilization Protects Against Alveolar Hemorrhage Through Amphiregulin and BATF-Mediated Regulatory T Cells

Fiona Mason,¹ Hui Xiong,² Ali Mobeen,¹ Md Saddam Hossain,¹ Sara Mahmudlu,¹ Rosanne Trevail,¹ Mikyal Mobeen,¹ Li Chen,³ Sunny Lee,¹ Tuncay Delibasi,⁴ Jyoti Misra Sen,⁵ and Mobin Karimi¹

Published January 27, 2026 - More info

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Abstract

Alveolar hemorrhage (AH) is a life-threatening condition with high mortality, yet the immunologic mechanisms governing disease severity remain poorly defined. Here, we demonstrate a protective role for T cell–intrinsic β-catenin stabilization in AH using a transgenic mouse model (CAT-Tg) in which β-catenin is stabilized under the Lck promoter. β-Catenin stabilization induced a distinct T cell phenotype marked by expansion of central effector memory cells (CD44⁺CD122⁺Eomes⁺T-bet⁺) and suppression of proinflammatory signaling, including reduced phosphorylation of STAT1, STAT3, and JAK1. Pristane-induced AH was attenuated in CAT-Tg mice, which exhibited reduced lung injury, decreased proteinuria, and diminished pulmonary proinflammatory cytokine production compared with wild-type controls. Protection was associated with a marked expansion of FOXP3⁺ regulatory T cells (Tregs). Mechanistically, β-catenin stabilization enhanced lung expression of Amphiregulin and BATF, mediators of Treg stability and tissue repair. Adoptive transfer of CAT-Tg–derived Tregs into wild-type mice conferred superior protection against AH, reducing lung inflammation and proteinuria. Transcriptomic analyses revealed enrichment of tissue repair and immune homeostasis pathways, including PI3K–Akt, angiogenesis, and STAT5 signaling. Collectively, these findings identify β-catenin as a regulator of a protective Amphiregulin–BATF–Treg axis, highlighting a immunomodulatory pathway with therapeutic potential for AH and inflammatory lung disease.

β-Catenin Stabilization Protects Against Alveolar Hemorrhage Through Amphiregulin and BATF-Mediated Regulatory T Cells

Fiona Mason,¹ Hui Xiong,² Ali Mobeen,¹ Md Saddam Hossain,¹ Sara Mahmudlu,¹ Rosanne Trevail,¹ Mikyal Mobeen,¹ Li Chen,³ Sunny Lee,¹ Tuncay Delibasi,⁴ Jyoti Misra Sen,⁵ and Mobin Karimi¹

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β-Catenin Stabilization Protects Against Alveolar Hemorrhage Through Amphiregulin and BATF-Mediated Regulatory T Cells

Fiona Mason,1 Hui Xiong,2 Ali Mobeen,1 Md Saddam Hossain,1 Sara Mahmudlu,1 Rosanne Trevail,1 Mikyal Mobeen,1 Li Chen,3 Sunny Lee,1 Tuncay Delibasi,4 Jyoti Misra Sen,5 and Mobin Karimi1

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Fiona Mason,¹ Hui Xiong,² Ali Mobeen,¹ Md Saddam Hossain,¹ Sara Mahmudlu,¹ Rosanne Trevail,¹ Mikyal Mobeen,¹ Li Chen,³ Sunny Lee,¹ Tuncay Delibasi,⁴ Jyoti Misra Sen,⁵ and Mobin Karimi¹