The IL-17 pathway intertwines with neurotrophin and TLR/IL-1R pathways since its domain shuffling origin.

Autor:	Chen S; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, China., Fan H; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Ran C; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Hong Y; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Feng H; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Yue Z; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Zhang H; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China., Pontarotti P; MEPHI (Microbes, Evolution, Phylogénie et Infection), Aix Marseille Université, Marseille, France., Xu A; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.; School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China., Huang S; State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 May 07; Vol. 121 (19), pp. e2400903121. Date of Electronic Publication: 2024 Apr 29.
DOI:	10.1073/pnas.2400903121
Abstrakt:	The IL-17 pathway displays remarkably diverse functional modes between different subphyla, classes, and even orders, yet its driving factors remains elusive. Here, we demonstrate that the IL-17 pathway originated through domain shuffling between a Toll-like receptor (TLR)/IL-1R pathway and a neurotrophin-RTK (receptor-tyrosine-kinase) pathway (a Trunk-Torso pathway). Unlike other new pathways that evolve independently, the IL-17 pathway remains intertwined with its donor pathways throughout later evolution. This intertwining not only influenced the gains and losses of domains and components in the pathway but also drove the diversification of the pathway's functional modes among animal lineages. For instance, we reveal that the crustacean female sex hormone, a neurotrophin inducing sex differentiation, could interact with IL-17Rs and thus be classified as true IL-17s. Additionally, the insect prothoracicotropic hormone, a neurotrophin initiating ecdysis in Drosophila by binding to Torso, could bind to IL-17Rs in other insects. Furthermore, IL-17R and TLR/IL-1R pathways maintain crosstalk in amphioxus and zebrafish. Moreover, the loss of the Death domain in the pathway adaptor connection to IκB kinase and stress-activated protein kinase (CIKSs) dramatically reduced their abilities to activate nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) in amphioxus and zebrafish. Reinstating this Death domain not only enhanced NF-κB/AP-1 activation but also strengthened anti-bacterial immunity in zebrafish larvae. This could explain why the mammalian IL-17 pathway, whose CIKS also lacks Death, is considered a weak signaling activator, relying on synergies with other pathways. Our findings provide insights into the functional diversity of the IL-17 pathway and unveil evolutionary principles that could govern the pathway and be used to redesign and manipulate it. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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