| First Author | Costa S | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 1049079 | PubMed ID | 36466913 |
| Mgi Jnum | J:331991 | Mgi Id | MGI:7407547 |
| Doi | 10.3389/fimmu.2022.1049079 | Citation | Costa S, et al. (2022) Neutrophils inhibit gammadelta T cell functions in the imiquimod-induced mouse model of psoriasis. Front Immunol 13:1049079 |
| abstractText | BACKGROUND: Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood. METHODS: In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development. RESULTS: By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and gammadelta T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and gammadelta T cell infiltration observed in neutrophil-depleted mice. CONCLUSIONS: Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells. |
