{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13"],"submitter":["Costa S"],"funding":["European Research Council"],"pubmed_abstract":["<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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."],"journal":["Frontiers in immunology"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9709482"],"repository":["biostudies-literature"],"pubmed_title":["Neutrophils inhibit γδ T cell functions in the imiquimod-induced mouse model of psoriasis"],"pmcid":["PMC9709482"],"funding_grant_id":["695714"],"pubmed_authors":["Zenaro E","Cestari T","Abram C","Bevilacqua D","Gasperini S","Lonardi S","De Sanctis F","Dusi S","Ugel S","Lowell C","Scapini P","Costa S","Caveggion E","Pettinella F","Constantin G","Girolomoni G","Rodegher P","Tagliaro F","Vermi W","Donini M","Cassatella M"],"additional_accession":[]},"is_claimable":false,"name":"Neutrophils inhibit γδ T cell functions in the imiquimod-induced mouse model of psoriasis","description":"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2025-04-05T10:17:03.362Z","creation":"2025-02-19T04:34:04.586Z"},"accession":"S-EPMC9709482","cross_references":{}}