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Keywords: asthma; asthma-COPD overlap; COPD; neutrophil; sputum EN asthma asthma-COPD overlap COPD neutrophil sputum 3137 3141 5 09/30/22 20221001 NES 221001 Soluble suppression of tumorigenicity 2 (sST2) is a decoy receptor for interleukin 33 (IL-33). Soluble ST2 enhances IL-33-induced neutrophilic and pro-type 2 inflammation in the lungs (C-E) Scatter plots of sST2 and IL-33 (C), IL-33 and chemokine (D), and sST2 and chemokine (E) levels in sputum from the same patients. [Extracted from the article]

Rationale: Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid‐resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C‐C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus‐associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib. Methods: We stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS‐2B cells with poly(I:C) along with interleukin‐13 (IL‐13) or IL‐4, and assessed CCL5 production. We also evaluated the signals involved in virus‐ and Th2‐cytokine‐induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production. Results: Poly(I:C) stimulated NHBE and BEAS‐2B cells to produce CCL5. Poly(I:C) and IL‐13 increased CCL5 production. Poly(I:C)‐induced CCL5 production occurred via the TLR3–IRF3 and IFNAR/JAK1–phosphoinositide 3‐kinase (PI3K) pathways, but not the IFNAR/JAK1–STATs pathway. In addition, IL‐13 did not augment poly(I:C)‐induced CCL5 production via the canonical IL‐13R/IL‐4R/JAK1–STAT6 pathway but likely via subsequent TLR3‐IRF3‐IFNAR/JAK1‐PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS‐2B cells than fluticasone propionate. Conclusion: We have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid‐resistant asthma with airway eosinophilia and persistent Th2‐type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy. [ABSTRACT FROM AUTHOR]

This article discusses the possible role of chitinase in regulating allergies in a mouse model exposed to diesel exhaust. The authors measured the expression of Ym1 and Ym2 mRNA in lung tissues by reverse transcription-polymerase chain reaction. They concluded that diesel exhaust particles induced Ym mRNA expression via a Th2 cell-biased response and airway hyperresponsiveness suggesting that chitinase may play an important role in responsiveness and airway inflammation and therefore may be involved in regulating allergic diseases.