Purpose: Vitiligo is a T cell-mediated skin depigmentation disease. Though treatments arresting disease progression and inducing repigmentation are available, the efficacy of these options is often limited and poorly sustained. How stromal signals contribute to the interferon-γ-dominant skin niches is unclear. This study aims to determine how fibroblasts participate in the IFN-γ-dominant vitiligo niche. Patients and methods: Mouse vitiligo models were established. Fibroblasts from control and vitiligo mice were extracted for RNA sequencing. In vitro IFN-γ stimulation was performed to verify the JAK-STAT pathway by qPCR and Western blot. T cell polarization with chemokines was measured by flow cytometry. Protein levels in tissues were also examined by IHC. Results: The vitiligo mouse model recapitulates the human CD8-IFN-γ pathway. RNA sequencing revealed elevated chemokine CCL2 and CCL8 in vitiligo fibroblast, which may be regulated by the JAK-STAT signaling. Such phenomenon is verified by JAK inhibitor peficitinib in vitro. Moreover, CCL2 addition into the naïve T polarization system promoted type 2 cytokines secretion, which represents a hallmark of vitiligo lesions. Conclusion: Dermal fibroblasts, a principal constituent of skin structure, respond to IFN-γ by skewing T cells towards a type 2 cytokine profile via CCL2 and CCL8, which can be abrogated by JAK inhibitor peficitinib.

Fibroblasts, critical for skin structure and function via extracellular matrix (ECM) production, undergo senescence linked to ECM changes and inflammation via senescence-associated secretory phenotypes (SASPs). Transforming growth factor (TGF-β), a pleiotropic cytokine, modulates fibroblast function through multiple signaling pathways, inducing cell cycle arrest, oxidative stress, DNA damage, and SASP production. These processes disrupt ECM homeostasis, exacerbate inflammation, and impair tissue repair, contributing to pathological skin changes. TGF-β induced fibroblast senescence involves multiple mechanisms and pathways. It causes cell cycle arrest by upregulating CDK inhibitors and activating the p53 pathway. TGF-β also promotes oxidative stress-induced senescence by increasing reactive oxygen species (ROS) production, activating pathways like SMAD, and causing DNA damage. In photoaging, UV exposure induces fibroblast senescence via TGF-β related mechanisms, reducing collagen production and increasing MMP levels. TGF-β also suppresses immune cell functions, creating an immunosuppressive microenvironment that accelerates cellular senescence. In refractory skin diseases like vitiligo, melanoma, and so on, TGF-β plays a complex role. Its abnormal activation drives fibroblast senescence, impacting immune responses and skin structure. However, Maintaining the normal expression of TGF-β preserves ECM homeostasis, promotes collagen synthesis, and reduces inflammatory factor expression. Emerging therapeutic strategies targeting TGF-β signaling show promise. Pharmaceutical agents and phototherapy mitigate senescence by modulating TGF-β pathways and thus suppress ROS, enhancing collagen synthesis. Combined approaches synergistically improve skin repair and elasticity. In summary, TGF-β significantly regulates fibroblast senescence in refractory skin diseases through various mechanisms and pathways. Its precise modulation could enhance skin repair and anti-aging therapies. However, further research is needed to explore the interactions between anti-aging ingredients and their clinical effects.

Background: Stroke, prevalent globally, particularly impacts low- and middle-income countries. Decreased lung function is one of the risk factors for stroke, and there is a lack of sufficient research on the association between the two, especially based on evidence from representative large samples. We aimed to explore the association between lung function and stroke incidence.Methods: We collected data from 13,371 participants from the 2007–2012 U.S. national cross-sectional study and 11,192 participants from the Chinese national cohort study during the 2011–2018 follow-up period. Multivariate logistic regression and Cox proportional hazards regression were used to assess cross-sectional and longitudinal associations of peak expiratory flow with stroke risks. Additionally, we used publicly available GWAS data from a European population to conduct Mendelian randomization analysis, further exploring the potential causal relationship.Results: The results of the cross-sectional study suggest that a decline in peak expiratory flow may be associated with an increased risk of stroke. The cohort study revealed that, compared to the first tertile group, the risk of stroke incidence in the second and third tertile groups of PEF decreased by 19% (hazard ratio (HR) = 0.810, 95%CI = 0.684–0.960) and 21.4% (HR = 0.786, 95%CI = 0.647–0.956), respectively. Mendelian randomization analysis clarified that higher PEF levels are significantly associated with a reduced risk of stroke (OR = 0.852, 95%CI = 0.727–0.997).Conclusion: Decreased lung function is a risk factor for stroke. As a simple and accurate indicator of lung function, PEF can be used to monitor lung function in community populations and patients for primary stroke prevention.

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single‐center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long‐term follow‐up data (6–120 months). It was found that 69.7% of patients achieved an excellent re‐color effect and 18.4% achieved a good re‐color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post‐operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR‐33‐23‐034502).