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Cross talk between T cells and airway smooth muscle (ASM) may play a role in modulating asthmatic airway inflammation and remodeling. Infiltrating T cells have been observed within the ASM bundles of asthmatics, and a wide range of direct and indirect interactions between T cells and ASM has been demonstrated using various in vitro and in vivo model systems. Contact-dependent mechanisms such as ligation and activation of cellular adhesion and costimulatory molecules, as well as the formation of lymphocyte-derived membrane conduits, facilitate the adhesion, bidirectional communication, and transfer of materials between T and ASM cells. T cell-derived cytokines, particularly of the Th1, Th2, and Th17 subsets, modulate the secretome, proliferation, and contractility of ASM cells. This review summarizes the mechanisms governing T cell-ASM cross talk in the context of asthma. Understanding the underlying mechanistic basis is important for directing future research and developing therapeutic interventions targeted toward this complex interaction. [ABSTRACT FROM AUTHOR]

In asthma, CD4+ T‐cell interaction with airway smooth muscle (ASM) may enhance its contractile properties and promote its proliferation. However, less is known about the effects of this interaction on T cells. To explore the consequences of interaction of CD4+ T cells with ASM we placed the cells in co‐culture and analyzed the phenotypic and functional changes in the T cells. Effector status as well as cytokine expression was assessed by flow cytometry. An increase in CD45RA−CD45RO+ memory T cells was observed after co‐culture; however, these cells were not more responsive to CD3/28 restimulation. A reduction in mitochondrial coupling and an increase in the production of mitochondrial reactive oxygen species by CD4+ T cells post‐restimulation suggested altered mitochondrial metabolism after co‐culture. RNA sequencing analysis of the T cells revealed characteristic downregulation of effector T‐cell‐associated genes, but a lack of upregulation of memory T‐cell‐associated genes. The results of this study demonstrate that ASM cells can induce a phenotypic shift in CD4+ T cells into memory‐like T cells but with reduced capacity for activation. [ABSTRACT FROM AUTHOR]

Asthmatic airways feature increased ASM mass that is largely attributable to hyperplasia, and which potentially contributes to excessive airway narrowing. T cells induce ASMC proliferation via contact‐dependent mechanisms in vitro that may have importance for asthmatic ASM growth, as CD4+ T cells infiltrate ASM bundles in asthmatic human airways. In this study, we used an in vitro migration assay to investigate the pathways responsible for the trafficking of human CD4+ T cells to ASM. ASMCs induced chemotaxis of activated CD4+ T cells, which was inhibited by the CXCR3 antagonist AMG487 and neutralizing antibodies against its ligands CXCL10 and 11, but not CCR3 or CCR5 antagonists. CXCR3 expression was upregulated among all T cells following anti‐CD3/CD28‐activation. CD4+ T cells upregulated CXCL9, 10, and 11 expression in ASMCs in an IFN‐γ/STAT1‐dependent manner. Disruption of IFN‐γ‐signaling resulted in reduced T cell migration, along with the inhibition of CD4+ T cell‐mediated STAT1 activation and CXCR3 ligand secretion by ASMCs. ASMCs derived from healthy and asthmatic donors demonstrated similar T cell‐recruiting capacities. In vivo CXCL10 and 11 expression by asthmatic ASM was confirmed by immunostaining. We conclude that the CXCL10/11‐CXCR3 axis causes CD4+ T cell recruitment to ASM that is amplified by T cell‐derived IFN‐γ. [ABSTRACT FROM AUTHOR]

Nepalese migrant workers are at heightened risk of adverse mental health problems. However, the social mechanisms by which experiences of labor migration create such vulnerabilities are not well understood. Moreover, limited attention has been paid to the experiences of left-behind spouses. This study explores how migrant fathers and left-behind mothers experience labor migration and how migration affects mental health across migrant household members, paying special attention to the role of gender. We conducted 29 in-depth interviews with Nepalese migrant fathers (N = 18) in South Korea and left-behind mothers (N = 11) in Nepal. Labor migration imposes substantial stress on the entire family. Migrant fathers discussed their feelings of guilt and worry regarding their relationships with their children due to physical and emotional distance. Left-behind mothers indicated loneliness and caregiver stress due to additional responsibilities as a single parent. Migrant fathers reported that they felt respected by their communities for their work, while left-behind mothers felt heavily scrutinized. Our findings highlight how labor migration reinforces gender inequalities in domestic responsibilities and norms regarding the expected roles of migrating men and left-behind women. These findings suggest that psychosocial services must be tailored to the unique needs of migrant workers and left-behind families. [ABSTRACT FROM AUTHOR]

In asthma, CD4 + T-cell interaction with airway smooth muscle (ASM) may enhance its contractile properties and promote its proliferation. However, less is known about the effects of this interaction on T cells. To explore the consequences of interaction of CD4 + T cells with ASM we placed the cells in co-culture and analyzed the phenotypic and functional changes in the T cells. Effector status as well as cytokine expression was assessed by flow cytometry. An increase in CD45RA - CD45RO + memory T cells was observed after co-culture; however, these cells were not more responsive to CD3/28 restimulation. A reduction in mitochondrial coupling and an increase in the production of mitochondrial reactive oxygen species by CD4 + T cells post-restimulation suggested altered mitochondrial metabolism after co-culture. RNA sequencing analysis of the T cells revealed characteristic downregulation of effector T-cell-associated genes, but a lack of upregulation of memory T-cell-associated genes. The results of this study demonstrate that ASM cells can induce a phenotypic shift in CD4 + T cells into memory-like T cells but with reduced capacity for activation., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Cystic fibrosis (CF) is a genetic disease that causes multiple airway abnormalities. Two major respiratory consequences of CF are airway hyperresponsiveness (AHR) and airway remodeling. Airway smooth muscle (ASM) is hypothesized to be responsible for the airway dysfunction, since their thickening is involved in remodeling, and excessive contraction by the ASM may cause AHR. It is unclear whether the ASM is intrinsically altered to favor increased contractility or proliferation or if microenvironmental influences induce pathological behavior in vivo. In this study, we examined the contractile and proliferative properties of ASM cells isolated from healthy donor and CF transplant lungs. Assays of proliferation showed that CF ASM proliferates at a higher rate than healthy cells. Through calcium analysis, no differences in contractile activation in response to histamine were found. However, CF ASM cells lagged in their reuptake of calcium in the sarcoplasmic reticulum. The combination CFTR corrector and potentiator, VX-809/770, used to restore CFTR function in CF ASM, resulted in a reduction in proliferation and in a normalization of calcium reuptake kinetics. These results show that impaired CFTR function in ASM cells causes intrinsic changes in their proliferative and contractile properties.