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J Leukoc Biol. 2017 Sep;102(3):791-803. doi: 10.1189/jlb.3MA0217-054RR. Epub 2017 Jun 22.

Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells.

Author information

1
Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.
2
Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
3
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chaoyang District, Beijing, China.
4
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
5
Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy.
6
Department of Laboratory Medicine, University of California, San Francisco, California, USA; and.
7
Division of Dermatology and Venereology, and University of Verona, Verona, Italy.
8
Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy; patrizia.scapini@univr.it.

Abstract

Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88fl/flVav-cre+ mice) with mice carrying the total MyD88 deficiency (Myd88-/- mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells. However, both Myd88-/- mouse strains developed some degree of epidermal thickening during the initial stages of IMQ-induced psoriasis, even in the absence of hematopoietic cell activation and infiltration into the skin, suggesting a contribution of MyD88-independent mechanisms in skin-resident stromal cells. With the use of conditional knockout mouse strains lacking MyD88 in distinct lineages of myeloid cells (Myd88fl/flLysM-cre+ and Myd88fl/flMRP8-cre+ mice), we report that MyD88 signaling in monocytes and Mϕ, but not in neutrophils, plays an important role in disease propagation and exacerbation by modulating their ability to sustain γδ T cell effector functions via IL-1β and IL-23 production. Overall, these findings add new insights into the specific contribution of skin-resident stromal vs. hematopoietic cells to disease initiation and progression in the IMQ-induced mouse model of psoriasis and uncover a potential novel pathogenic role for monocytes/Mϕ to psoriasis development.

KEYWORDS:

monocytes/macrophages; neutrophils; skin inflammation

PMID:
28642279
DOI:
10.1189/jlb.3MA0217-054RR
[Indexed for MEDLINE]

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