A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes

Abstract In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yo Okamura, Hiroshi Miyanishi, Masato Kinoshita, Tomoya Kono, Masahiro Sakai, Jun-ichi Hikima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e352f1cbbb6345aaa7428dfeb60b8e2e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e352f1cbbb6345aaa7428dfeb60b8e2e
record_format	dspace
spelling	oai:doaj.org-article:e352f1cbbb6345aaa7428dfeb60b8e2e2021-12-02T17:30:34ZA defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes10.1038/s41598-021-91534-32045-2322https://doaj.org/article/e352f1cbbb6345aaa7428dfeb60b8e2e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91534-3https://doaj.org/toc/2045-2322Abstract In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (IL-17RA1, an IL-17A/F receptor) in Japanese medaka (Oryzias latipes) using genome editing technique, and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparison of gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. Conversely, expression of genes related to cardiovascular system development, including fli1a, sox7, and notch1b in the anterior intestine, and that of genes related to oxidation–reduction processes including ugp2a, aoc1, and nos1 in posterior intestine was up-regulated in IL-17RA1-KO medaka. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.Yo OkamuraHiroshi MiyanishiMasato KinoshitaTomoya KonoMasahiro SakaiJun-ichi HikimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yo Okamura Hiroshi Miyanishi Masato Kinoshita Tomoya Kono Masahiro Sakai Jun-ichi Hikima A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
description	Abstract In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (IL-17RA1, an IL-17A/F receptor) in Japanese medaka (Oryzias latipes) using genome editing technique, and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparison of gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. Conversely, expression of genes related to cardiovascular system development, including fli1a, sox7, and notch1b in the anterior intestine, and that of genes related to oxidation–reduction processes including ugp2a, aoc1, and nos1 in posterior intestine was up-regulated in IL-17RA1-KO medaka. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.
format	article
author	Yo Okamura Hiroshi Miyanishi Masato Kinoshita Tomoya Kono Masahiro Sakai Jun-ichi Hikima
author_facet	Yo Okamura Hiroshi Miyanishi Masato Kinoshita Tomoya Kono Masahiro Sakai Jun-ichi Hikima
author_sort	Yo Okamura
title	A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
title_short	A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
title_full	A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
title_fullStr	A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
title_full_unstemmed	A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
title_sort	defective interleukin-17 receptor a1 causes weight loss and intestinal metabolism-related gene downregulation in japanese medaka, oryzias latipes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e352f1cbbb6345aaa7428dfeb60b8e2e
work_keys_str_mv	AT yookamura adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT hiroshimiyanishi adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT masatokinoshita adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT tomoyakono adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT masahirosakai adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT junichihikima adefectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT yookamura defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT hiroshimiyanishi defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT masatokinoshita defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT tomoyakono defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT masahirosakai defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes AT junichihikima defectiveinterleukin17receptora1causesweightlossandintestinalmetabolismrelatedgenedownregulationinjapanesemedakaoryziaslatipes
_version_	1718380760653627392

A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes

Ejemplares similares