AUTHOR=Herster Franziska , Bittner Zsofia , Codrea Marius Cosmin , Archer Nathan K. , Heister Martin , Löffler Markus W. , Heumos Simon , Wegner Joanna , Businger Ramona , Schindler Michael , Stegner David , Schäkel Knut , Grabbe Stephan , Ghoreschi Kamran , Miller Lloyd S. , Weber Alexander N. R. TITLE=Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01867 DOI=10.3389/fimmu.2019.01867 ISSN=1664-3224 ABSTRACT=

Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.