ProjectProject C10 - Platelets as novel contributors to psoriasis skin autoinflammation

Basic data

Title:
Project C10 - Platelets as novel contributors to psoriasis skin autoinflammation
Duration:
01/07/2023 to 30/06/2027
Abstract / short description:
Psoriasis is an inflammatory autoimmune disease characterized by skin lesions with massive infiltration of immune cells and is frequently also associated with cardiovascular co-morbidities. Especially polymorphonuclear neutrophils (PMNs) drive psoriatic skin inflammation but how they home to the skin and are modulated in their activity remains unclear. In an unbiased screen of 332 surface antigens on primary human blood PMNs, the Weber lab identified platelet surface antigens as a defining feature of psoriasis PMNs due to a significantly increased formation of platelet-neutrophil complexes (PNCs) in psoriasis patients. Surprisingly, in psoriatic but not in healthy skin, platelets were detected in direct contact with PMNs. Similarly, in the topical imiquimod (IMQ)-induced mouse model of psoriasis, disease induction promoted PNC formation and platelet skin homing. Importantly, in vivo depletion of circulating platelets ameliorated skin disease severity significantly and completely abrogated PMN skin homing and neutrophil extracellular trap (NET) release. Thus, platelets appear to be novel contributors to psoriasis pathology and disease severity. As the mechanism and dynamics of platelet skin homing are unknown, we will firstly address how, mechanistically, platelets infiltrate into the psoriatic skin in the localized IMQ-induced skin inflammation. Secondly, we will explore which of the pleiotropic functions described for platelets (degranulation, cytokine release, migration, sensitization of PMN) apply to platelets found in psoriasis skin lesions and how their activity affects keratinocytes, dermal fibroblasts and infiltrating immune cells other than PMN.

Involved staff

Managers

Faculty of Medicine
University of Tübingen
Research training group: Non-canonical G protein signaling pathways
Research training groups

Contact persons

Interfaculty Institute for Cell Biology (IFIZ)
Interfaculty Institutes

Local organizational units

Department of Preclinical Imaging and Radiopharmacy
Department of Radiology
Hospitals and clinical institutes, Faculty of Medicine

Funders

Bonn, Nordrhein-Westfalen, Germany
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