Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus

A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a...

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Autores principales:	Tom Aschman, Sandra Schaffer, Stylianos Iason Biniaris Georgallis, Antigoni Triantafyllopoulou, Peter Staeheli, Reinhard E. Voll
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SLE lupus type III interferons <i>Ifnlr1</i> interferon lambda pristane Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/936f250686fe4ba3bc38e5efd943088c
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spelling	oai:doaj.org-article:936f250686fe4ba3bc38e5efd943088c2021-11-11T17:12:03ZInterferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus10.3390/ijms2221117471422-00671661-6596https://doaj.org/article/936f250686fe4ba3bc38e5efd943088c2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11747https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (<i>Ifnlr1</i><sup>−/−</sup>) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, <i>Ifnlr1</i><sup>−/−</sup> mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115<sup>+</sup>Ly6C<sup>+</sup>) were reduced in pristane-treated <i>Ifnlr1</i><sup>−/−</sup> mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.Tom AschmanSandra SchafferStylianos Iason Biniaris GeorgallisAntigoni TriantafyllopoulouPeter StaeheliReinhard E. VollMDPI AGarticleSLElupustype III interferons<i>Ifnlr1</i>interferon lambdapristaneBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11747, p 11747 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SLE lupus type III interferons <i>Ifnlr1</i> interferon lambda pristane Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	SLE lupus type III interferons <i>Ifnlr1</i> interferon lambda pristane Biology (General) QH301-705.5 Chemistry QD1-999 Tom Aschman Sandra Schaffer Stylianos Iason Biniaris Georgallis Antigoni Triantafyllopoulou Peter Staeheli Reinhard E. Voll Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
description	A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (<i>Ifnlr1</i><sup>−/−</sup>) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, <i>Ifnlr1</i><sup>−/−</sup> mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115<sup>+</sup>Ly6C<sup>+</sup>) were reduced in pristane-treated <i>Ifnlr1</i><sup>−/−</sup> mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.
format	article
author	Tom Aschman Sandra Schaffer Stylianos Iason Biniaris Georgallis Antigoni Triantafyllopoulou Peter Staeheli Reinhard E. Voll
author_facet	Tom Aschman Sandra Schaffer Stylianos Iason Biniaris Georgallis Antigoni Triantafyllopoulou Peter Staeheli Reinhard E. Voll
author_sort	Tom Aschman
title	Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
title_short	Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
title_full	Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
title_fullStr	Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
title_full_unstemmed	Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus
title_sort	interferon lambda regulates cellular and humoral immunity in pristane-induced lupus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/936f250686fe4ba3bc38e5efd943088c
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Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus

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