IL-1R1 Signaling Facilitates Munro’s Microabscess Formation in Psoriasiform Imiquimod-Induced Skin Inflammation

Autor: Mireia Uribe-Herranz, Liselotte E. Jensen, Katelynn A. Milora, Li-Hua Lian, Kirsten M. Hooper
Rok vydání: 2013
Předmět:
Zdroj: The Journal of investigative dermatology
ISSN: 0022-202X
DOI: 10.1038/jid.2012.512
Popis: Munro’s microabscesses contain polymorphonuclear leukocytes and form specifically in the epidermis of psoriasis patients. The mechanism whereby the neutrophils are recruited into the epidermis is poorly understood. Using a combination of human and mouse primary keratinocyte cell cultures and the imiquimod-induced psoriasis-like mouse model of skin inflammation we explored the role of interleukin-1 (IL-1) signaling in microabscess formation. In vitro imiquimod stimulated production of IL-1α and neutrophil recruiting chemokines. Imiquimod activated chemokine expression was dependent upon adenosine signaling and independent of IL-1α and IL-1 receptor type 1 (IL-1R1); nevertheless, IL-1α could enhance chemokine expression initiated by imiquimod. Topical application of imiquimod in vivo led to epidermal microabscess formation, acanthosis and increased IL-1α and chemokine expression in the skin of wild type mice. However, in IL-1R1 deficient mice these responses were either absent or dramatically reduced. These results demonstrate that IL-1α and IL-1R1 signaling is essential for microabscess formation, neutrophil recruiting chemokine expression and acanthosis in psoriasis-like skin inflammation induced by imiquimod.
Databáze: OpenAIRE