What question did this study set out to answer?

This study aims to understand how epidermal MHC-II influences NK cell recruitment and contributes to keratinocyte pyroptosis in psoriasis.

May 10, 2026Open Access

Epidermal MHC-II-mediated NK cell recruitment triggers keratinocyte pyroptosis, facilitating pathogenesis of psoriasis

Key Points

This study aims to understand how epidermal MHC-II influences NK cell recruitment and contributes to keratinocyte pyroptosis in psoriasis.
Used anti-MHC-II treatment and H2-Ab1 knockout in the epidermis to assess effects on psoriatic dermatitis.
Applied spatial transcriptomics to analyze keratinocyte and NK cell interactions in psoriatic lesions.
Conducted multicolor immunohistochemistry to examine correlations between MHC-II expression and NK cell activity.
NK cell infiltration significantly increased in psoriatic skin lesions.
Epidermal H2-Ab1 deletion reduced NK cell and keratinocyte communication, lowering pyroptosis.
MHC-II expression positively correlated with NK cell infiltration and granzyme B levels.

Abstract

Abstract Psoriasis is a chronic inflammatory disease characterized by dysregulated interactions between keratinocytes (KCs) and immune cells. However, the details of KCs orchestrating the immune cell infiltration, particularly for natural killer (NK) cells, remain unclear. Here NK cell infiltration is significantly increased in psoriatic skin lesions, and the application of anti-MHC-II treatment or knockout of H2-Ab1 in the epidermis dramatically reduces IMQ-mediated psoriatic dermatitis as well as the infiltration of NK cells through CXCL10 mediated by the ERK–CREB axis. Spatial transcriptomics reveal that NK cells coexist with KCs, driven by enhanced CXCL signaling, and epidermal H2-Ab1 deletion suppresses KC–NK cell communication. NK cells release granzyme B, inducing pyroptosis in adjacent GSDME-expressing KCs, contributing to the inflammatory response. NK cell depletion or Gsdme knockout reduces pyroptosis and alleviates psoriasis-like dermatitis. Multicolor immunohistochemistry confirms that epidermal MHC-II expression in psoriatic lesions correlates positively with NK cell, granzyme B and cleaved-GSDME levels. This study reveals that epidermal MHC-II attracts NK cells, triggering KC pyroptosis and remodeling the immune microenvironment in psoriasis, offering novel insights into its pathogenesis.

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