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The potential of signal regulatory protein alpha as a therapeutic target for airway hyperreactivity 9433

Year: 2025

Type: article

Abstract: Description The study investigated the role of Group 2 innate lymphoid cell (ILC2) function in the context of mitochondrial metabolism, with a focus on the regulatory dynamics between activating and inhibitory molecules. The investigation explored the potential of the inhibitory molecule signal-regulated protein α (SIRPα) as a novel therapeutic target for the management of ILC2-mediated airway hyperreactivity (AHR). The findings demonstrated that the activation of SIRPα using CD47Fc effectively suppressed ILC2 function, leading to a substantial improvement in AHR. This therapeutic effect was demonstrated to suppress type 2 cytokine production by regulating mitochondrial metabolism without modulating lipid or glucose metabolism. Furthermore, in a study using human ILC2s (hILC2s), it was found that SIRPα regulates hILC2 activation by regulating mitochondrial metabolism. The hILC2 results also corroborated the findings obtained in mice, where AHR was significantly suppressed by CD47-Fc administration in the humanized mice. Notably, SIRPα expression in hILC2s was elevated in asthmatics and correlated with disease severity. Furthermore, expression of SIRPα in hILC2 was inversely correlated with the forced expiratory volume in one second in asthmatic patients, suggesting that SIRPα is not only a potential therapeutic target but also a prognostic predictor of asthma. In conclusion, these findings suggest that targeting SIRPα might be a promising therapeutic strategy for allergic asthma. Funding Sources National Institutes of Health grant : R01 HL144790, R01 HL151493, R01 AI145813, R01AI169687, R01 HL151769, and R01 HL 159804 (OA) Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.2832