Yumin Xia

Pemphigus relapse shows a nonrandom, site-specific pattern, with recurrent lesions preferentially occurring at previously affected anatomical locations. In a retrospective cohort of 105 patients, we found that spatial overlap between new-onset and relapse sites significantly exceeded random expectation and was independent of circulating autoantibody levels. Recurrent lesions were enriched for CD4+CD69+ and CD8+CD103+ tissue-resident memory T cells, suggesting a role for localized immune memory in disease recurrence.

Background: Targeted systemic therapies for atopic dermatitis (AD), including biologics and Janus kinase inhibitors, are increasingly used. However, comparative postmarketing evidence on herpetic infection-related safety signals across these therapies remains limited. Objectives: To compare safety signals of herpetic infections associated with targeted AD therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: FAERS reports (Q2 2017 to Q1 2025) involving dupilumab, abrocitinib, baricitinib or upadacitinib were included if these agents were designated as the primary suspect drug and the indication was AD. Disproportionality analyses using four algorithms were performed to detect signals for overall and virus-specific herpetic events. Subgroup analyses by age, sex and time to onset (TTO) were conducted. Results: All therapies demonstrated positive signals for herpetic infections. Baricitinib and abrocitinib showed the strongest signals, followed by upadacitinib, whereas dupilumab showed comparatively lower signals overall. Notably, dupilumab demonstrated a herpes simplex virus (HSV) signal comparable with abrocitinib and higher than for upadacitinib, and a signal for eczema herpeticum (EH) was also identified. Signals were generally higher in female patients, except for upadacitinib. Age-stratified analyses showed varying signal patterns across age groups. The median TTO differed between therapies, with an earlier onset for upadacitinib. Conclusions: Reporting patterns of herpetic infections differ across targeted AD therapies. Disproportionate reporting of HSV and EH with dupilumab warrants further investigation. Differences across sex, age and TTO suggest potential heterogeneity in reporting patterns, which may reflect underlying patient characteristics and reporting behaviours.

Objective: Cardiac involvement is a major cause of morbidity in systemic lupus erythematosus (SLE). Tumor necrosis factor–like weak inducer of apoptosis (TWEAK) is elevated in SLE, but its contribution to lupus‐associated cardiac injury is unclear. We investigated the role of TWEAK/fibroblast growth factor–inducible 14 (Fn14) signaling in SLE‐related cardiomyopathy and its potential as a biomarker and therapeutic target. Methods: Serum TWEAK, inflammatory cytokines, autoantibodies, and oxidative stress markers were measured in 242 patients with SLE and 66 age‐ and sex‐matched controls, with correlation to echocardiographic, electrocardiographic, and myocardial enzyme findings. Cardiac pathology and redox signaling were assessed in pristane‐induced lupus models using wild‐type mice and mice deficient of Fn14 by histopathology, immunoblotting, immunofluorescence, and quantitative proteomics. Direct effects of TWEAK on mitochondrial oxidative stress, antioxidant signaling, and apoptosis were examined in primary cardiomyocytes isolated from MRL/lpr mice who were lupus prone. Results: Serum TWEAK levels were significantly elevated in patients with SLE and were highest in those with cardiac abnormalities compared with healthy controls. TWEAK correlated positively with malondialdehyde, 8‐hydroxy‐2’‐deoxyguanosine, disease activity, and inflammatory cytokines and inversely with superoxide dismutase. Elevated baseline TWEAK predicted new cardiac abnormalities during follow‐up and declined with clinical improvement. In mice with lupus, Fn14 deficiency reduced cardiac reactive oxygen species accumulation, restored Nrf2/HO‐1 antioxidant signaling, attenuated histopathological injury, and preserved cardiac function. In vitro, TWEAK induced mitochondrial superoxide production, suppressed Nrf2 signaling, and promoted apoptosis in lupus‐prone cardiomyocytes. Conclusion: TWEAK/Fn14 signaling drives oxidative stress–mediated cardiomyocyte injury in SLE and represents a promising biomarker and therapeutic target for lupus‐associated cardiac damage. image

Background: Atopic dermatitis (AD) patients exhibit a paradox of impaired skin barrier with intense itching, yet often demonstrate rapid re‐epithelialization after scratching. While basophils are key effector cells in allergic inflammation, their role in the subsequent tissue repair remains unexplored. Objective: We investigated whether basophils, recruited during sensitized skin responses, contribute to wound healing. Methods: Using single‐cell RNA sequencing, flow cytometry, and immunofluorescence, we mapped basophil infiltration and activation in sensitizer (oxazolone)‐induced skin injury models. We employed genetic ( Mcpt8 ^CT/+ R26 ^DTA/+ ) and antibody‐mediated (anti‐FcεRI) basophil depletion, as well as basophil‐specific Il4/Il13 knockout mice ( Il4/13 ^fl/fl Mcpt8 ^CT/+ ) to define their functional contribution. Macrophage polarization was assessed by flow cytometry, RT‐qPCR, and immunohistochemistry. Results: We identified a significant enrichment of basophils in wounded skin, peaking at day 3–6 post‐injury. Sensitizer‐challenge enhanced basophil recruitment and accelerated wound closure, angiogenesis, and re‐epithelialization. Depletion of basophils severely impaired these repair processes. Mechanistically, basophils were the predominant source of IL‐4 and IL‐13 in the early wound microenvironment. These cytokines were essential for driving macrophage polarization toward a pro‐repair M2 phenotype. Loss of IL4/IL13 specifically in basophils phenocopied the healing defects observed in basophil‐deficient mice, and this could be rescued by local cytokine administration. Conclusion: Our study uncovers a novel pro‐repair function of basophils in sensitizer‐exposed skin. Beyond their well‐known role in provoking itch and inflammation, basophils are critical for initiating type 2 immune‐mediated tissue regeneration via IL‐4/IL‐13‐dependent macrophage reprogramming. This axis represents a promising therapeutic target for chronic wounds, particularly in the context of allergic skin disorders.

Background The complement system critically mediates systemic lupus erythematosus (SLE) pathogenesis through dual mechanisms: promoting inflammatory organ damage while regulating the initiation of immune tolerance. Among its three activation pathways (classical, alternative, and lectin), the lectin pathway is the most recently characterized. Findings The lectin pathway engages pattern-recognition molecules (PRMs: mannose-binding lectin [MBL], collectins, ficolins) and mannose-binding lectin–associated serine proteases (MASPs). These components orchestrate unique biological functions beyond canonical complement activation, including self-antigen clearance, B/T-cell tolerance modulation, and interferon-α production. PRM/MASP genetic variants (particularly loss-of-function genotypes) predispose to SLE and associate with organ-specific damage phenotypes. PRMs detect damage-associated molecular patterns on apoptotic cells, initiating complement activation. Resulting fragments (C3a, C5a) and membrane attack complexes directly drive tissue injury. Clinically, circulating PRM/MASP levels and tissue deposition patterns reflect disease activity and organ involvement. Although MASP-2- and C5-targeting monoclonal antibodies demonstrate therapeutic potential in trials, most lectin pathway interventions remain preclinical. Conclusions This review integrates clinical correlations, mechanistic advances in both complement-dependent and complement-independent functions, and emerging SLE therapeutics targeting the lectin pathway.

Cutaneous wound healing consists of complex processes involving different types of cells and signalling pathways, and occurs in three phases (inflammatory, proliferative and tissue remodelling). The dysregulation of these processes leads to abnormal wound healing, manifesting as hard-to-heal (chronic) wounds at one extreme and pathological scarring at the other. Recent studies have shown that the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signalling pathway regulates inflammatory, re-epithelialisation, collagen synthesis and angiogenesis processes, suggesting that it can modulate cutaneous wound healing. Despite numerous studies suggesting a relationship between the TWEAK/Fn14 axis and cutaneous wound healing, there has been little attention paid to this relationship to date. There is scarce direct evidence supporting that TWEAK/Fn14 axis-targeted therapies work in cutaneous wounds. This review summarises the evidence that TWEAK/Fn14 signalling is involved in wound repair as well as in tissue remodelling. In addition, TWEAK/Fn14 axis-targeted therapies in other diseases are highlighted, and their therapeutic potential in cutaneous wounds discussed.

The healing of diabetic skin wounds is often delayed due to cellular dysfunction and oxidative stress. Recently, cold atmospheric plasma (CAP) has shown promising efficacy in treating diabetic wounds; however, its exact mechanism remains unclear. The study aimed to investigate the effect of CAP on fibroblast growth factor‐inducible 14 (Fn14) signaling‐mediated hair follicle stem cell (HFSC) functionality, which may contribute to the healing of diabetic wounds. In vitro experiments were conducted to analyze the effect of CAP treatment on HFSC proliferation, cytokine production, and reactive oxygen species (ROS)‐related protein expressions. Animal experiments were performed to verify the effect of CAP treatment on a mouse type 1 diabetic wound model. CAP enhanced both Fn14 expression and HFSC proliferation, accompanied by the activation of the Wnt/β‐catenin signaling pathway. Expressions of Sirt1, Nrf2, hypoxia‐inducible factor‐1α, and Sox9, which were initially suppressed under high glucose conditions, were significantly restored upon CAP stimulation. Moreover, CAP‐activated hydrogel promoted diabetic wound healing in this mouse model. Furthermore, inhibition of Fn14 abrogated the promotive effect of CAP intervention. Fn14 signaling is a key mediator, mechanistically linking CAP to HFSC activation and tissue repair. These findings provide a therapeutic blueprint for CAP‐based regeneration of diabetic wounds.