Clec7a-mediated regulation of Killer-like Lectin Receptor expression controls T cell immunity

Abstract

Abstract Clec7a is a C-type lectin receptor (CLR) originally defined for its non-redundant role in anti-fungal immunity. Subsequent work has broadened this view, implicating Clec7a in host defense against diverse pathogens and in the pathogenesis of cancer, autoimmunity, neuroinflammation, and developmental disorders. How a single innate receptor orchestrates such wide-ranging outcomes remains unresolved. We previously demonstrated that dendritic cell (DC)-expressed Clec7a is required for protective anti-fungal immunity in the gastrointestinal tract through regulation of fungus-specific CD4⁺ T cell responses. Here, we show that Clec7a controls the expression of multiple C-type lectins in DCs, including a cluster of killer lectin-like receptors (KLRs). Notably, we reveal that these KLRs directly regulate DC function and control CD4⁺ T cell responses. These findings define a novel Clec7a-KLR axis that integrates innate and adaptive immunity, highlighting a regulatory pathway with broad relevance for immune homeostasis, inflammation, and host defense.

Affiliated Institutions

• University of Zurich CH
• Phillips Exeter Academy US
• University of Exeter GB
• Institute of Immunology HR
• Chiba University JP
• Queen Mary University of London GB
• University of Birmingham GB

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