Sonntag Thomas, Omi Shizue, Andreeva Antonina, Valotteau Claire, Eichelbrenner Jeanne, Chisholm Andrew D, Ward Jordan D, Pujol Nathalie
Aix Marseille Univ, INSERM, CNRS, CIML, Turing Centre for Living Systems, Marseille, France.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
PLoS Genet. 2025 Mar 20;21(3):e1011593. doi: 10.1371/journal.pgen.1011593. eCollection 2025 Mar.
Apical extracellular matrices (aECMs) act as crucial barriers, and communicate with the epidermis to trigger protective responses following injury or infection. In Caenorhabditis elegans, the skin aECM, the cuticle, is produced by the epidermis and is decorated with periodic circumferential furrows. We previously showed that mutants lacking cuticle furrows exhibit persistent immune activation (PIA), providing a valuable model to study the link between cuticle damage and immune response. In a genetic suppressor screen, we identified spia-1 as a key gene downstream of furrow collagens and upstream of immune signalling. spia-1 expression oscillates during larval development, peaking between each moult together with patterning cuticular components. It encodes a secreted protein that localises to furrows. SPIA-1 shares a novel cysteine-cradle domain with other aECM proteins. SPIA-1 mediates immune activation in response to furrow loss and is proposed to act as an extracellular signal activator of cuticle damage. This research provides a molecular insight into intricate interplay between cuticle integrity and epidermal immune activation in C. elegans.
顶端细胞外基质（aECMs）起着关键屏障的作用，并与表皮进行沟通，以在损伤或感染后触发保护反应。在秀丽隐杆线虫中，皮肤aECM即角质层，由表皮产生，并带有周期性的环形沟纹。我们之前表明，缺乏角质层沟纹的突变体表现出持续免疫激活（PIA），这为研究角质层损伤与免疫反应之间的联系提供了一个有价值的模型。在一项遗传抑制因子筛选中，我们确定spia-1是沟纹胶原蛋白下游和免疫信号上游的关键基因。spia-1的表达在幼虫发育过程中振荡，在每次蜕皮之间达到峰值，同时与角质层结构成分一致。它编码一种定位于沟纹的分泌蛋白。SPIA-1与其他aECM蛋白共享一个新的半胱氨酸支架结构域。SPIA-1介导对沟纹缺失的免疫激活，并被认为是角质层损伤的细胞外信号激活剂。这项研究为秀丽隐杆线虫角质层完整性与表皮免疫激活之间的复杂相互作用提供了分子层面的见解。
