{"doi":"10.3389/fimmu.2025.1563469","title":"Editorial: Unraveling the molecular mechanisms of cytokine signaling in regulating inflammatory diseases","abstract":"Chronic and dysregulated inflammation is a hallmark of many autoimmune and inflammatory diseases, significantly impacting patient health and quality of life. Despite their prevalence, the intricate molecular mechanisms underlying cytokine regulation in these conditions remain poorly understood. This special issue aims to bridge this knowledge gap by exploring the complex network of cytokine signaling pathways and their roles in immunoregulation during inflammatory diseases. Through a collection of nine research articles and six review articles, we delve into the latest discoveries and insights, providing a comprehensive overview of the current state of research in this critical area.Cambon et. al. investigates the cytokine profiles in the lung compartment of COVID-19 patients, particularly those with acute respiratory distress syndrome (C-ARDS). They evaluated caspase-1 activation, IL-1 signature, and other inflammatory cytokine pathways using post-mortem lung tissues, bronchoalveolar lavage fluids (BALF), and serum. Their findings reveal elevated levels of proinflammatory molecules included caspase-1, IL-1β, IL-1Ra, IL-6, IFN-γ, and CXCL-10 in BALF from steroid-treated C-ARDS patients, highlighting the predominant IL-1β/IL-6 signature and IFNγ-associated chemokines despite steroid treatment. This study underscores the potential of targeting these pathways to improve treatment response and limit lung damage in ARDS.In another study, Vorobyeva DA et. al. developed an ex vivo model of SARS-CoV-2 lung infection to study cytokine production. Their findings reveal elevated concentrations of proinflammatory mediators, namely G-CSF, GM-CSF, GRO-a, IFN-γ, IL-6, IL-8, IP-10, MCP-3, MIP-1a, PDGF-AA, and VEGF in infected lung tissue, reflecting the cytokine alterations observed in COVID-19 patients. This model provides a valuable platform for investigating SARS-CoV-2 infection mechanisms and testing antiviral drugs.The study by Bédard-Matteau J. et. al. identifies IL-17F as a key cytokine associated with severe COVID-19. Elevated IL-17F levels were found in severe cases, promoting neutrophil adhesion to endothelial cells via ERK1/2 and p38 MAPK-dependent pathways. These findings highlight the potential of targeting IL-17F signaling to mitigate neutrophilic inflammation and immunothrombosis in severe COVID-19.Von Stemann et. al. examine the association of cytokine autoantibodies (c-aAb) with community-acquired pneumonia (CAP). They measured c-aAb targeting various cytokines in plasma samples from 665 CAP patients. The results indicate that high-titer type 1 IFN c-aAb are more prevalent in men with SARS-CoV-2 infection, while GM-CSF c-aAb are associated with asthma and bronchiectasis comorbidities in men. These findings suggest that c-aAb specificity, comorbidity, and sex influence clinical outcomes in CAP, providing insights for personalized treatment strategies.The research by Yang et. al. investigates the therapeutic potential of myeloid-derived growth factor (MYDGF) in primary Sjögren's syndrome (pSS). Using a mouse model, they demonstrated that MYDGF treatment alleviates pSS symptoms by increasing salivary flow rate, reducing lymphocyte infiltration, and promoting M2 macrophage polarization. The study identifies the suppression of the CX3CL1/CX3CR1 axis as a key mechanism, suggesting MYDGF as a promising therapeutic target for pSS.The research by Lee et. al. explores the role of pregnane X receptor (PXR) in particulate matter (PM)-induced inflammation in atopic dermatitis (AD). Their findings indicate that PXR activation reduces type 17 inflammation by inhibiting the NF-κB pathway, suggesting PXR as a therapeutic target for controlling PM-induced AD aggravation. In addition, Xu et. al. review the emerging roles of protease-activated receptor 2 (PAR2) in various skin conditions, including atopic dermatitis, psoriasis, vitiligo, and melasma. The review highlights PAR2's involvement in the cutaneous microenvironment and associated comorb","journal":"Frontiers in Immunology","year":2025,"id":556016,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1454817,"name":"Huawei Mao","orcid":"0000-0001-8807-9267","position":1,"is_corresponding":false},{"id":251050,"name":"Wai Po Chong","orcid":"0000-0001-9640-199X","position":2,"is_corresponding":false},{"id":1454816,"name":"Jian Zheng","orcid":"0000-0002-1999-8566","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:03.976486Z","pmid":"40007545","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}