title: IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome.
abstract: The pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL-1 family. Here we report overexpression of IL-1α, IL-1β, and IL-1 receptor antagonist mRNA, associated to expression of IL-23p19, IL-17A, and IL-22 in skin cells, upon topical application of the TLR7 agonist imiquimod (IMQ) in C57BL/6J mice. IMQ-induced skin inflammation was partially reduced in mice deficient for both IL-1α/IL-1β or for IL-1 receptor type 1 (IL-1R1), but not in IL-1α- or IL-1β-deficient mice, demonstrating the redundant activity of IL-1α and IL-1β for skin inflammation. NLRP3 or apoptosis-associated Speck-like protein containing a Caspase recruitment domain-deficient mice had no significant reduction of skin inflammation in response to IMQ treatment, mainly due to the redundancy of IL-1α. However, IMQ-induced skin inflammation was abolished in the absence of MyD88, the adaptor protein shared by IL-1R and TLR signaling pathways. These results are consistent with the TLR7 dependence of IMQ-induced skin inflammation. Thus, IL-1R1 contributes to the IMQ-induced skin inflammation, and disruption of MyD88 signaling completely abrogates this response.
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
authors.forename: Hanitriniaina
authors.initials: H
authors.lastname: Rabeony
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Pohin
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.|CHU de Poitiers, Poitiers, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vasseur
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.|CHU de Poitiers, Poitiers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit-Paris
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jégou
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Favot
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.|CHU de Poitiers, Poitiers, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Frouin
authors.affiliation: INSERM - UN UMR 957, Faculté de Médecine de Nantes, 1 rue Gaston Veil, Nantes cedex, France.
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Boutet
authors.affiliation: INSERM - UN UMR 957, Faculté de Médecine de Nantes, 1 rue Gaston Veil, Nantes cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: ArtImmune SAS, Orléans, France.
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.affiliation: INEM UMR 7355 CNRS and Université d'Orléans, France and IIDMM, University of Cape Town, RSA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.|BIOAlternatives, Gençay, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Bernard
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.|CHU de Poitiers, Poitiers, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morel
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000634:Aminoquinolines / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003875:Drug Eruptions / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000077271:Imiquimod; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D002352:Carrier Proteins; D016207:Cytokines; C583355:IL1R1 protein, mouse; D058847:Inflammasomes; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053573:Receptors, Interleukin-1 Type I; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000077271:Imiquimod
keywords: IL-1R; Imiquimod; MyD88; NLRP3 inflammasome; Skin inflammation