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: Hanitriniaina Rabeony, Mathilde Pohin, Philippe Vasseur, Isabelle Petit-Paris, Jean-François Jégou, Laure Favot, Eric Frouin, Marie-Astrid Boutet, Frédéric Blanchard, Dieudonnée Togbe, Bernhard Ryffel, François-Xavier Bernard, Jean-Claude Lecron, Franck Morel
• Journal: European journal of immunology (Eur J Immunol) Vol. 45 Issue 10 Pg. 2847-57 (Oct 2015) ISSN: 1521-4141 [Electronic] Germany
• PMID: 26147228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Adjuvants, Immunologic
• Aminoquinolines
• Carrier Proteins
• Cytokines
• IL1R1 protein, mouse
• Inflammasomes
• Membrane Glycoproteins
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Receptors, Interleukin-1 Type I
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Imiquimod

Topics

• Adjuvants, Immunologic (adverse effects, pharmacology)
• Aminoquinolines (adverse effects, pharmacology)
• Animals
• Carrier Proteins (genetics, immunology)
• Cytokines (genetics, immunology)
• Drug Eruptions (genetics, immunology, pathology)
• Imiquimod
• Inflammasomes (genetics, immunology)
• Membrane Glycoproteins (genetics, immunology)
• Mice
• Mice, Knockout
• Myeloid Differentiation Factor 88 (genetics, immunology)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Receptors, Interleukin-1 Type I (genetics, immunology)
• Signal Transduction (drug effects, genetics, immunology)
• Skin (immunology, pathology)
• Toll-Like Receptor 7 (genetics, immunology)