title: IL-1R1 signaling facilitates Munro's microabscess formation in psoriasiform imiquimod-induced skin inflammation.
abstract: 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 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.
authors: Department of Microbiology and Immunology and Temple Autoimmunity Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors: Mireia
authors: M
authors: Uribe-Herranz
authors: Li-Hua
authors: LH
authors: Lian
authors: Kirsten M
authors: KM
authors: Hooper
authors: Katelynn A
authors: KA
authors: Milora
authors: Liselotte E
authors: LE
authors: Jensen
mesh_terms: D000038:Abscess / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D054360:Chemokine CXCL1 / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D020405:Dermis / Q000166:cytology; D003875:Drug Eruptions / Q000276:immunology* / Q000473:pathology; D000078404:Epidermal Cells; D006801:Humans; D000077271:Imiquimod; D053582:Interleukin-1alpha / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D000077271:Imiquimod