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

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

Author information

1
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, POITIERS, France.
2
CHU de Poitiers, Poitiers, France.
3
INSERM - UN UMR 957, Faculté de Médecine de Nantes, 1 rue Gaston Veil, Nantes cedex, France.
4
ArtImmune SAS, Orléans, France.
5
INEM UMR 7355 CNRS and Université d'Orléans, France and IIDMM, University of Cape Town, RSA.
6
BIOAlternatives, Gençay, France.

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.

KEYWORDS:

IL-1R; Imiquimod; MyD88; NLRP3 inflammasome; Skin inflammation

PMID:
26147228
DOI:
10.1002/eji.201445215
[Indexed for MEDLINE]
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