Imiquimod-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome
European Journal of Immunology, 45(7):2847-2857
RABEONY H., POHIN M., VASSEUR P., PETIT-PARIS I., JÉGOU JF., FAVOT L., FROUIN E., BOUTET MA., BLANCHARD F., TOGBE D., RYFFEL B., BERNARD FX., LECRON JC., MOREL F. (2015)
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, France.
CHU de Poitiers, France.
INSERM – UN UMR 957, Faculté de Médecine de Nantes, 1 rue Gaston Veil, Nantes Cedex, France.
ArtImmune SAS, Orléans, France.
INEM UMR 7355 CNRS and Université d’Orléans, France and IIDMM, University of Cape Town, RSA.
Bioalternatives, Gençay, France.
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.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
KEYWORDS: IL-1R; Imiquimod; MyD88; NLRP3 inflammasome; Skin inflammation
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