Dr. Leonhard Heinz
MedUni Wien RESEARCHER OF THE MONTH June 2021
TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9
Toll-like receptors (TLRs) are important sensor proteins of the immune system that detect pathogen-associated molecular patterns, such as bacterial cell wall components or viral nucleic acids. Receptor signaling relies on specific downstream adaptor proteins that are required to regulate the immune response. In this study, we have identified a novel adaptor protein, TASL, that is genetically associated with systemic lupus erythematosus and that connects endosomal TLRs with the pro-inflammatory transcription factor IRF5. Mechanistically, TASL harbors an activation motif necessary for IRF5 recruitment to the receptor complex and subsequent transcriptional activation. This discovery provides a molecular explanation for the involvement of TASL in autoimmunity and highlights this pathway as a new potential target for pharmacologic intervention.
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