The efficacy and immunological effects of upadacitinib in the treatment of moderate-to-severe Chinese atopic dermatitis patients.

Upadacitinib has received approval for the treatment of atopic dermatitis (AD) with favorable response in clinical trials. However, real-world research on its efficacy remains relatively limited. To bridge this gap, we conducted a prospective cohort study involving 25 Chinese patients with moderate-to-severe AD. These patients received a daily dose of 15 mg of upadacitinib. Our objective was to assess the real-world efficacy of upadacitinib and its impact on the immune system. Clinical assessments were conducted at baseline, 4 weeks, 8 weeks, and 12 weeks following treatment initiation. The findings revealed that upadacitinib treatment significantly improved the clinical scores of the patients. Regarding immunological markers, upadacitinib led to a significant reduction in peripheral blood eosinophils, as well as a decrease in neutrophil count. Furthermore, upadacitinib treatment resulted in an overall decrease in Th1, Th2, and Th17/22-type cytokines, as well as other inflammatory factors. Importantly, for the first time, we observed a notable reduction in both IL-22+CD4+ T cells and serum IL-22 levels in all treated patients, including those with recalcitrant AD who had previously shown inadequate responses to systemic treatments like dupilumab. Currently, international guidelines position upadacitinib as a second-line option following the failure of systemic treatments like dupilumab. Our findings provide valuable insights into the real-world effectiveness and immunological impacts of upadacitinib, which can aid in better understanding and implementation of the drug in clinical practice.

Interleukin-33 deficiency exacerbated experimental autoimmune encephalomyelitis with an influence on immune cells and glia cells.

Interleukin (IL)-33, a member of the IL-1 cytokine family, is highly expressed in central nervous system (CNS), suggesting its potential role in CNS. Although some studies have focused on the role of IL-33 in multiple sclerosis (MS) / experimental autoimmune encephalomyelitis (EAE), an autoimmune disease characterized by demyelination and axonal damage in CNS, the exact role of IL-33 in MS/EAE remains unclear and controversial. Here, we used IL-33 knockout mice to clarify the role of endogenous IL-33 in EAE by simultaneously eliminating its role as a nuclear transcription factor and an extracellular cytokine. We found that the clinical score in IL-33 knockout EAE mice was higher accompanied by more severe demyelination compared with the wild-type (WT) EAE mice. As for the main immune cells participating in EAE in IL-33 knockout mice, pathogenic effector T cells increased both in peripheral immune organs and CNS, while CD4+FOXP3+ regulatory T cells decreased in spleen and lymph nodes, Th2 cells and natural killer (NK) cells decreased in CNS. Additionally, the populations of microglia/macrophages and CD11C+CD11B+ dendritic cells (DCs) increased in CNS of IL-33 knockout mice with EAE, among which iNOS-producing microglia/macrophages increased. Moreover, resident astrocytes/microglia were more activated in IL-33 knockout mice with EAE. In vitro, after blocking the IL-33, the proliferation of primary astrocytes, the production of MCP-1/CCL2 and TNF-α by astrocytes, and the production of TNF-α by primary microglia stimulated by the homogenate of the peak stage of EAE were increased. Our results indicate that IL-33 plays a protective role in EAE and exerts extensive influences on multiple immune cells and neural cells involved in EAE.