IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome

Eur J Immunol. 2015 Oct;45(10):2847-57. doi: 10.1002/eji.201445215. Epub 2015 Jul 24.


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.

Keywords: IL-1R; Imiquimod; MyD88; NLRP3 inflammasome; Skin inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • 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