CD48 regulates ILC2 effector function and lung inflammation through the PKCß pathway 2049

Abstract Description   Th2 cytokines play a significant role in the onset and development of asthma, leading to increased interest in the function of group 2 innate lymphoid cells (ILC2). Targeting ILC2 regulation presents a promising strategy for allergic asthma treatment. CD48, a member of the signaling lymphocyte activation molecule family, modulates immune cell activity. This study demonstrates that CD48 expression is upregulated in activated ILC2s, with high levels correlating with increased ILC2 activation. Conversely, deletion or inhibition of CD48 in ILC2s suppresses their activation and cytokine production. Adoptive transfer experiments using CD48 deficient ILC2s in alymphoid mice revealed significant alleviation of airway hyperreactivity when compared to the wild-type control. RNA sequencing analysis indicated diminished PI3K signaling and reduced PKCβ gene expression in CD48KO ILC2s. Additionally, both activators and inhibitors of PKCβ were found to modulate ILC2 activation and effector function. Moreover, validation in peripheral human ILC2s showed that stimulation enhances CD48 expression, while CD48 inhibition suppresses ILC2 activation and cytokine production. In conclusion, targeting CD48 on ILC2s represents a novel therapeutic strategy for asthmatic patients who do not adequately respond to existing treatments. This research enhances our understanding of the molecular mechanisms underlying ILC2-mediated inflammation in asthma and provides new insights for therapeutic intervention. Funding Sources National Institutes of Health Public Health Service grants R01 HL144790, R01 HL151493, R01 AI145813, R01 AI169687, R01 HL151769, and R01 HL159804 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)