Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids

Abstract Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regul...

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Autores principales:	Joannie M. Allaire, Anita Poon, Shauna M. Crowley, Xiao Han, Zohreh Sharafian, Navjit Moore, Martin Stahl, Brian Bressler, Pascal M. Lavoie, Kevan Jacobson, Xiaoxia Li, Bruce A. Vallance
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15d2427d54394e72ab94d917fb2ea064
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spelling	oai:doaj.org-article:15d2427d54394e72ab94d917fb2ea0642021-12-02T18:02:57ZInterleukin-37 regulates innate immune signaling in human and mouse colonic organoids10.1038/s41598-021-87592-22045-2322https://doaj.org/article/15d2427d54394e72ab94d917fb2ea0642021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87592-2https://doaj.org/toc/2045-2322Abstract Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.Joannie M. AllaireAnita PoonShauna M. CrowleyXiao HanZohreh SharafianNavjit MooreMartin StahlBrian BresslerPascal M. LavoieKevan JacobsonXiaoxia LiBruce A. VallanceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joannie M. Allaire Anita Poon Shauna M. Crowley Xiao Han Zohreh Sharafian Navjit Moore Martin Stahl Brian Bressler Pascal M. Lavoie Kevan Jacobson Xiaoxia Li Bruce A. Vallance Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
description	Abstract Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.
format	article
author	Joannie M. Allaire Anita Poon Shauna M. Crowley Xiao Han Zohreh Sharafian Navjit Moore Martin Stahl Brian Bressler Pascal M. Lavoie Kevan Jacobson Xiaoxia Li Bruce A. Vallance
author_facet	Joannie M. Allaire Anita Poon Shauna M. Crowley Xiao Han Zohreh Sharafian Navjit Moore Martin Stahl Brian Bressler Pascal M. Lavoie Kevan Jacobson Xiaoxia Li Bruce A. Vallance
author_sort	Joannie M. Allaire
title	Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
title_short	Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
title_full	Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
title_fullStr	Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
title_full_unstemmed	Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
title_sort	interleukin-37 regulates innate immune signaling in human and mouse colonic organoids
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15d2427d54394e72ab94d917fb2ea064
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Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids

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