Pulmonary fibrosis (PF) is a serious and often fatal illness that occurs in various clinical settings and represents a significant unmet medical need. Increasing evidence indicates that neutrophil extracellular traps (NETs) contribute significantly to the progression of PF. Therefore, understanding the pathways by which NETs contribute to the disease is crucial for developing effective treatments. This review focuses on the formation of NETs and the common mechanisms of NETs in PF.

The aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance. A total of 38 SLE patients and 33 healthy volunteers were recruited. Real time PCR and western blotting were performed to determine mRNA and protein levels of NEK7, NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the two groups. ELISA was used to detect serum levels of IL-1b and IL-18. The same methods were used to detect changes in the above indices in the 25 SLE patients after treatment. Correlations between clinical and laboratory parameters were also analyzed. Compared to those in healthy controls, levels of NEK7, NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18 were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were inversely correlated with disease activity, whereas a positive correlation was observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3 increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase-1, IL-1b, and IL-18. Results indicate that the expression of the NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is inversely correlated with disease activity. A positive effect of NEK7 on NLRP3 was observed, and the low expression of NLRP3 in SLE patients might be related to the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates the maturation and release of IL-1b and IL-18, and contributes to the pathogenesis of SLE and LN.

Introduction: Humoral immunity plays a key role in the pathogenesis of autoimmune diseases, and B-lymphocyte activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are essential for the maintenance of B-lymphocyte reservoirs and humoral immunity. In March 2021, telitacicept, the world’s first dual target three-channel biologic, was approved in China for the treatment of SLE and is currently in clinical trials exploring multiple indications for other autoimmune diseases. Areas Covered: This article summarizes the mechanism of action, pharmacokinetics, and clinical efficacy of telitacicept for the treatment of multiple autoimmune diseases. Expert Opinion: So far, the efficacy and safety of telitacicept in autoimmune diseases have been fully demonstrated in clinical practice. There are still many unresolved issues regarding the timing of initiation and discontinuation, still needs to be evaluated in future studies.

Background: Rapidly progressive interstitial lung disease (RP-ILD) is the most serious complication of anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5⁺ DM). This study was performed to assess the prognostic factors of patients with anti-MDA5⁺ DM and the clinical characteristics and predictors of anti-MDA5⁺ DM in combination with RP-ILD.Methods: In total, 73 MDA5⁺ DM patients were enrolled in this study from March 2017 to December 2021. They were divided into survival and non-survival subgroups and non-RP-ILD and RP-ILD subgroups.Results: The lactate dehydrogenase (LDH) concentration and prognostic nutritional index (PNI) were independent prognostic factors in patients with anti-MDA5⁺ DM: the elevated LDH was associated with increased mortality (p = 0.01), whereas the elevated PNI was associated with reduced mortality (p < 0.001). The elevated LDH was independent risk prognostic factor for patients with anti-MDA5⁺ DM (HR 2.42, 95% CI: 1.02–4.83, p = 0.039), and the elevated PNI was independent protective prognostic factor (HR, 0.27; 95% CI, 0.08 - 0.94; p = 0.039). Patients who had anti-MDA5⁺ DM with RP-ILD had a significantly higher white blood cell count and LDH concentration than those without RP-ILD (p = 0.007 and p = 0.019, respectively). In contrast, PNI was significantly lower in patients with RP-ILD than those without RP-ILD (p < 0.001). The white blood cell count and elevated LDH were independent and significant risk factors for RP-ILD (OR 1.54, 95% CI: 1.12 - 2.13, p = 0.009 and OR 8.68, 95% CI: 1.28 - 58.83, p = 0.027, respectively), whereas the lymphocyte was an independent protective factor (OR, 0.11; 95% CI, 0.01 - 0.81; p = 0.03).Conclusion: The elevated LDH and elevated PNI were independent prognostic factors for patients with anti-MDA5⁺ DM. The elevated LDH was independent risk factor for RP-ILD. Patients with anti-MDA5⁺ DM could benefit from the measurement of LDH and PNI, which are inexpensive and simple parameters that could be used for diagnosis as well as prediction of the extent of lung involvement and prognosis.

Alveolar epithelial cells play an essential role in the initiation and progression of pulmonary fibrosis, and the occurrence of epithelial–mesenchymal transition (EMT) may be the early events of pulmonary fibrosis. Recent studies have shown chemokines are involved in the complex process of EMT, and CXC chemokine ligand 16 (CXCL16) is also associated with many fibrosis-related diseases. However, whether CXCL16 is dysregulated in alveolar epithelial cells and the role of CXCL16 in modulating EMT in pulmonary fibrosis has not been reported. In this study, we found that CXCL16 and its receptor C-X-C motif chemokine receptor 6 (CXCR6) were upregulated in bleomycin induced EMT in human alveolar type II-like epithelial A549 cells. Synergistic effect of CXCL16 and bleomycin in promoting EMT occurrence, extracellular matrix (ECM) excretion, as well as the pro-inflammatory and pro-fibrotic cytokines productions in A549 cells were observed, and those biological functions were impaired by CXCL16 siRNA. We further confirmed that CXCL16 regulated EMT in A549 cells via the TGF-β1/Smad3 pathways. These results indicated that CXCL16 could promote pulmonary fibrosis by promoting the process of EMT via the TGF-β1/Smad3 signaling pathway.