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Researchers Identify C1QBP Protein Checkpoint in Fungal Immunity

A study shows C1QBP blocks an epigenetic pathway required for interleukin-1β production during systemic Candida albicans infections in mice.

WHAT YOU NEED TO KNOW
  • C1QBP stops phosphorylated protein kinase C δ from entering the nucleus, blocking DOT1L-mediated histone H3 lysine 79 trimethylation at the Il1b locus.
  • Depleting C1QBP in dendritic cells increased interleukin-1β secretion and enhanced T helper 17 cell responses in mice.
  • The study was conducted by researchers at Shanghai Tenth People’s Hospital and published in Nature Communications on August 14, 2026.

Researchers identified Complement C1q binding protein, known as C1QBP, as a critical negative regulator that represses interleukin-1β production during fungal infections, according to a peer-reviewed study published in Nature Communications. Dendritic cell-derived interleukin-1β drives antifungal immune defense following Dectin-1 recognition of fungal β-glucan, countering high-mortality invasive candidiasis caused primarily by Candida albicans.

C1QBP suppresses this immune pathway by sequestering phosphorylated protein kinase C δ within the cytoplasm, preventing the kinase from moving into the cell nucleus. Under standard activation, nuclear phosphorylated protein kinase C δ stimulates the RNF20/RNF40 ubiquitin ligase complex. That complex then recruits the methyltransferase DOT1L to catalyze histone H3 lysine 79 trimethylation at the Il1b gene locus, enabling transcription.

Testing in animal models confirmed that dendritic cell-specific depletion of C1QBP increases interleukin-1β secretion. This targeted removal amplified protective T helper 17 cell responses and improved survival resistance in mice challenged with systemic C. albicans infections.

Hui Wang, Yi-Heng Yang, Jia-Jie Tang, Yebo Gu, Xin-Ming Jia, and colleagues at Tongji University's Shanghai Tenth People’s Hospital conducted the investigation with data analysis support from Kaiqing Li at Shanghai OE Biotech Co. The project received backing from the National Natural Science Foundation of China and the National Key Research and Development Program of China before its publication on August 14, 2026.

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