Neutrophils inhibit γδ T cell functions in the imiquimod-induced mouse model of psoriasis.

Autor:	Costa S; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Bevilacqua D; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Caveggion E; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Gasperini S; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Zenaro E; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Pettinella F; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Donini M; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Dusi S; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Constantin G; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Lonardi S; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Vermi W; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., De Sanctis F; Division of Immunology, University of Verona, Verona, Italy., Ugel S; Division of Immunology, University of Verona, Verona, Italy., Cestari T; Division of Immunology, University of Verona, Verona, Italy., Abram CL; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States., Lowell CA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States., Rodegher P; Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy., Tagliaro F; Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy., Girolomoni G; Division of Dermatology and Venereology, University of Verona, Verona, Italy., Cassatella MA; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy., Scapini P; Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Nov 15; Vol. 13, pp. 1049079. Date of Electronic Publication: 2022 Nov 15 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1049079
Abstrakt:	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 γδ 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 γδ 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Costa, Bevilacqua, Caveggion, Gasperini, Zenaro, Pettinella, Donini, Dusi, Constantin, Lonardi, Vermi, De Sanctis, Ugel, Cestari, Abram, Lowell, Rodegher, Tagliaro, Girolomoni, Cassatella and Scapini.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu