AUTHOR=Costa Sara , Bevilacqua Dalila , Caveggion Elena , Gasperini Sara , Zenaro Elena , Pettinella Francesca , Donini Marta , Dusi Stefano , Constantin Gabriela , Lonardi Silvia , Vermi William , De Sanctis Francesco , Ugel Stefano , Cestari Tiziana , Abram Clare L. , Lowell Clifford A. , Rodegher Pamela , Tagliaro Franco , Girolomoni Giampiero , Cassatella Marco A. , Scapini Patrizia 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1049079

DOI=10.3389/fimmu.2022.1049079

ISSN=1664-3224

ABSTRACT=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. In this study, we utilized the imiquimod (IMQ)-induced mouse model of psoriasis to elucidate the specific contribution of neutrophils to psoriasis development. 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. 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.