New Paper - A11 Lee-Kirsch
24.01.2024
New publication from Min Ae Lee-Kirsch´s group
This study by Min Ae and colleagues identifies pathogenic variants in UNC93B1 that selectively dysregulate TLR7-dependent RNA sensing, leading to severe early-onset autoimmunity. By combining human genetics with functional analyses, the authors show that these variants lower TLR7 ligand-binding and signaling thresholds, resulting in exaggerated sensing of self-RNA and loss of immune tolerance. The findings establish UNC93B1 as a critical rheostat of the TLR7 axis, controlling the discrimination between self and non-self RNA, and provide direct human genetic evidence that precise quantitative tuning of TLR7-mediated nucleic acid sensing is essential for immune homeostasis. Moreover, the study reveals actionable pathways for targeted therapeutic intervention.
Published in Science Immunology:
https://www.science.org/doi/10.1126/sciimmunol.adi9769
