NMI promotes the secretion of IL-17 and exacerbates psoriasis.

Abstract

Damage-associated molecular patterns (DAMPs) are well established as key mediators of innate immune activation; however, their functions in modulating adaptive immunity, particularly T cell responses, remain incompletely characterized. Here, we report the identification and functional characterization of NMI-a recently identified DAMP-as a regulator of T helper 17 (Th17) cell activity and its involvement in psoriasis pathogenesis. Elevated expression of NMI was observed in psoriatic skin lesions and correlated significantly with heightened IL-17 levels. In a murine model of psoriasis, <i>Nmi</i> deficiency (<i>Nmi</i>^-/-) resulted in a marked attenuation of skin inflammation, accompanied by significantly reduced expression of IL-17A and IL-17F. In vitro studies further demonstrated that NMI promotes the secretion of IL-17A and IL-17F from differentiated Th17 cells through its interaction with Toll-like receptor 4. Moreover, therapeutic neutralization of NMI using specific antibodies effectively ameliorated psoriatic symptoms in mice. Collectively, these results identify NMI as an endogenous enhancer of Th17-mediated immunity and highlight its potential as a therapeutic target in psoriasis.