| First Author | Costa S | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 102 |
| Issue | 3 | Pages | 791-803 |
| PubMed ID | 28642279 | Mgi Jnum | J:247751 |
| Mgi Id | MGI:5925803 | Doi | 10.1189/jlb.3MA0217-054RR |
| Citation | Costa S, et al. (2017) Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells. J Leukoc Biol 102(3):791-803 |
| abstractText | 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 Mvarphi, but not in neutrophils, plays an important role in disease propagation and exacerbation by modulating their ability to sustain gammadelta T cell effector functions via IL-1beta 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/Mvarphi to psoriasis development. |
