Tasl-KO Mouse

TASL, short for TLR adaptor interacting with SLC15A4 on the lysosome, is an innate immune adaptor protein crucial for endolysosomal TLR7/8/9 signaling. It binds to the endolysosomal transporter SLC15A4 and activates IRF5, triggering the transcription of type I interferons and cytokines, which is vital for pathogen recognition and immune responses [1,2]. It also plays a role in maintaining epidermal homeostasis by regulating keratinocyte proliferation and differentiation [3].

Loss-of-function studies show that TASL deficiency abrogates responses to endolysosomal TLR agonists in human immune cells, specifically impairing the activation of the IRF pathway without affecting NF-κB and MAPK signalling [1]. In keratinocytes, TASL deficiency hinders proliferation and migration through G1/S cell cycle arrest and disrupts the differentiation process by affecting lysosomal function and calcium modulation [3].

In conclusion, TASL is essential for innate immune responses via TLR7-9 signalling and for keratinocyte biology. Its role in these processes is revealed through loss-of-function experiments. Understanding TASL could potentially offer new therapeutic strategies for autoimmune diseases like systemic lupus erythematosus and improve our knowledge of keratinocyte-related biological processes [1,3].

References:

1. Heinz, Leonhard X, Lee, JangEun, Kapoor, Utkarsh, Rebsamen, Manuele, Superti-Furga, Giulio. 2020. TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. In Nature, 581, 316-322. doi:10.1038/s41586-020-2282-0. https://pubmed.ncbi.nlm.nih.gov/32433612/

2. Chen, Xudong, Xie, Min, Zhang, Sensen, Rebsamen, Manuele, Yang, Maojun. 2023. Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling. In Nature communications, 14, 6627. doi:10.1038/s41467-023-42210-9. https://pubmed.ncbi.nlm.nih.gov/37863913/

3. Park, Ji Yeong, Kim, Hyeng-Soo, Hyung, Hyejin, Jang, Soyoung, Ryoo, Zae Young. 2024. TASL mediates keratinocyte differentiation by regulating intracellular calcium levels and lysosomal function. In Scientific reports, 14, 10978. doi:10.1038/s41598-024-61674-3. https://pubmed.ncbi.nlm.nih.gov/38744928/