The CARD14sh-BCL10-MALT 1 complex regulates MAVS- mediated antiviral response in keratinocytes

• 成果类型: Article
• 署名作者: Zerillo, Lucrezia; Zotti, Tiziana; Tutela, Angelapia; Madera, Jessica Raffaella; Grasso, Gabriella; Vito, Pasquale; Stilo, Romania
• 署名单位: University of Sannio
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9640
• DOI: 10.1073/pnas.2500711122
• 发表日期: 2025-06-17
• 关键词: malt1 protease

摘要

The Mitochondrial Antiviral Signaling Protein (MAVS) is a key adaptor in antiviral immunity, mediating type I interferon responses downstream of RIG1 and TLR3. While MAVS regulation is essential for antiviral defense, its modulation in keratinocytes is poorly understood. Here, we examine the role of the CARD14-BCL10-MALT1 (CBM) complex, a skin-specific signaling module, in controlling MAVS-dependent antiviral responses. We identify CARD14short as a dual regulator that activates NF-kappa B while inhibiting IRF3 signaling. Psoriasis-associated CARD14 mutations are less efficient in restricting IRF3 activation and cytokine production upon Poly (I:C) stimulation, highlighting a potential mechanism in psoriasis pathogenesis. BCL10 is essential for MAVS-induced IRF3 activation, while MALT1 limits IRF3 signaling by promoting MAVS cleavage, K48-linked ubiquitination, and proteasomal degradation. Genetic and chemical inhibition of MALT1 enhances IRF3 activation and type I IFN expression. These findings reveal a MAVS-CBM regulatory network linking innate immunity to epithelial homeostasis.