IFNγ, IL-4, and IL-13 upregulate IL-31 receptor alpha in airway smooth muscle cells to induce airway hyperresponsiveness in asthma

• Published in: The Journal of immunology (1950) Vol. 210; no. 1_Supplement; pp. 67 - 67.18
• Main Authors: akkenapally, santhoshi vani, Yombo, Dan JK, geereddy, Bhanuprakash reddy, Madala, Satish K
• Format: Journal Article
• Language: English
• Published: 01.05.2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.210.Supp.67.18

Abstract Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. AHR is a major cause of hospitalization, morbidity, and mortality in allergic asthma. Both Th1 and Th2 cytokines, including IFN-γ, IL-4, and IL-13 have been shown to induce AHR; however, the underlying mechanisms remain unclear. We observed a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31 during house dust mite- and Schistosoma mansoni soluble egg antigen-induced allergic asthma. In support of this, IFN-γ and Th2 cytokines, IL-4 and IL-13, upregulated IL-31RA but not IL-31 in airway smooth muscle cells (ASMC). Importantly, the deficiency of IL-31RA was sufficient to attenuate contractility of ASMC and allergen-induced AHR but had no effect on inflammation and goblet cell hyperplasia. Similarly, the loss of IL31RA attenuated both IFNγ and IL13-induced AHR with limited changes in inflammation and goblet cell hyperplasia. Importantly, suggesting a mechanism for direct regulation of ASMC contractility, IL-31RA increased muscarinic acetylcholine receptor 3 (CHRM3) expression and calcium signaling. Together, these results suggest an important role for IL-31RA in the regulation of ASMC contractility and AHR distinct from airway inflammation and goblet cell hyperplasia in asthma. This research was supported by NIH NHLBI grants 1R01HL157176 and 5R01HL134801