Biology subjects

Mobeen, A.

Publications and source records attributed to Mobeen, A..

3 recordsLinked to original sources

bioRxiv2026

ITK Deficiency Attenuates Alveolar Hemorrhage by Enhancing Regulatory T Cell-Mediated Tissue Resilience

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 establish ITK as a regulator of the balance between pulmonary injury and reparative immunity and support targeting the ITK axis in severe inflammatory lung disease.

immunology↗

bioRxiv2025

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

Pulmonary hemorrhaging (PH) is a life-threatening condition with a high mortality rate, yet the role of immune cells in its pathogenesis remains poorly defined. Here, we investigated the protective function of {beta}-catenin stabilization in T cells and its impact on PH. Using a novel transgenic mouse model (CAT-Tg) with stabilized {beta}-catenin, we demonstrate that {beta}-catenin stabilization induces a distinct T-cell phenotype characterized by an expansion of central effector memory cells (CD44, CD122, Eomes, T-bet). Mechanistically, this effect was associated with suppression of key proinflammatory pathways, including reduced phosphorylation of STAT1, STAT3, and JAK1. PH was induced using pristane, and CAT-Tg mice were significantly protected from lung damage, showing reduced proteinuria and decreased pulmonary proinflammatory cytokine production compared with wild-type (WT) and T cell-specific {beta}-catenin knockout (cKO) mice. This protection correlated with a marked increase in FOXP3 regulatory T cells (Tregs) in CAT-Tg mice. We further identified a novel mechanism in which {beta}-catenin stabilization enhances lung expression of Amphiregulin and BATF, two molecules essential for Treg function and tissue repair. Adoptive transfer of CAT-Tg Tregs into WT mice with pristane-induced PH conferred superior protection, as evidenced by reduced lung inflammation and proteinuria. The systemic administration of a {beta}-catenin agonist to mice with PH significantly attenuated disease severity. Our bioinformatic analysis confirmed that {beta}-catenin stabilization upregulates pathways associated with tissue repair and immune homeostasis, including PI3K-Akt, angiogenesis, and STAT5 signaling. Collectively, these findings reveal that {beta}-catenin stabilization protects against pulmonary hemorrhage by inducing a specialized T-cell phenotype and establishing a protective Amphiregulin-BATF-Treg axis. This study identifies a novel immunomodulatory pathway with therapeutic potential for PH and other inflammatory lung diseases.

immunology↗

bioRxiv2020

Modeling the post-translational modifications and its effects in the NF-κB pathway

The transcriptional activities of NFKB1 and NFKB2 complexes are regulated by several post-translational modifications at different sites of these complexes. The post-translational modifications reported in the literature include phosphorylation, methylation, acetylation, sulphydration, nitrosylation, ubiquitination and sumoylation. We present a pathway network model with 172 proteins, 313 molecular species and 476 reactions including degradation of IkB (NFKBIA), proteolytic processing, and posttranslational modifications on p65 (RELA), RELB, p50 (NFKB1), and p52 (NFKB2) proteins. Comparing with experimental data on the over expression or knockouts of specific genes afforded qualitative agreement between model predictions and the experimental results. NFKB1:RELA complex is activated by active IKBKB, PIN1, MAP3K14 but repressed by PPARG and PDLIM2. MAP3K14 and UBE2I enhance the NFKB2:RELB activity, whereas NLRP12 is its repressor. The constitutive activation of NFKB1 complex through positive regulation of group of cytokines (IL1, IL1B and IL6) and IKK complex (alpha, beta and gamma) could be annulled by activation of PPARG, PIAS3 and P50-homodimer together instead of individual activations. Thus, the presented network pathway model has predictive utility in inferring NF-{kappa}B activity.

systems biology↗