We’re excited to share our new data on the SLC15A4-TASL complex, now published in Cell Reports!

In this article, our PhD student Haobo Zhang demonstrates that the transport function of SLC15A4, previously proposed to affect TLR7–9 activation, is dispensable to assemble an IRF5-activating complex with TASL. Here, we show that the essential role of SLC15A4 is to recruit TASL to endolysosomes, while its transport activity is not needed when TASL is tethered to this compartment.

Highlights:

• Fusion of TASL to transport-deficient SLC15A4 rescues TLR7–9 responses
• Endolysosomal-tethered TASL restores TLR7–9 signaling in SLC15A4-deficient cells
• The SLC15A4-TASL complex is required for TLR7–9-induced IRF5 in human B cells
• The role of SLC15A4 in TLR7–9 pathways is to act as a scaffold for TASL recruitment

This work was performed thanks to our amazing team, the SNSF funding and the support of our colleagues at Department of Immunobiology at UNIL.

Citation: Haobo Zhang, Léa Bernaleau, Maeva Delacrétaz, Ed Hasanovic, Ales Drobek, Hermann Eibel, Manuele Rebsamen; SLC15A4 controls endolysosomal TLR7–9 responses by recruiting the innate immune adaptor TASL. Cell Reports 29 August 29 August 2023, 42(8): 112916. doi: https://doi.org/10.1016/j.celrep.2023.112916