Deregulated PSGL-1 Expression in B Cells and Dendritic Cells May Be Implicated in Human Systemic Sclerosis Development

• Published in: Journal of investigative dermatology Vol. 138; no. 10; pp. 2123 - 2132
• Main Authors: Silván, Javier, González-Tajuelo, Rafael, Vicente-Rabaneda, Esther, Pérez-Frías, Alicia, Espartero-Santos, Marina, Muñoz-Callejas, Antonio, García-Lorenzo, Elena, Gamallo, Carlos, Castañeda, Santos, Urzainqui, Ana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018
• Subjects: ILD; SSc; cDC; A8pDC; dcSSc; lcSSc; CA; pDC; DC
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2018.04.003

Systemic sclerosis (SSc) is an autoimmune disorder with high morbidity and mortality, is difficult to diagnose early, and has no curative treatment. PSGL-1 is a leukocyte receptor whose deficiency in mice promotes an SSc-like disease. ADAM8, a metalloprotease that cleaves PSGL-1, is implicated in inflammatory processes. Our goal was to evaluate whether PSGL-1 and ADAM8 contribute to the pathogenesis of human SSc. We found that patients with SSc presented increased PSGL-1 expression on monocytes, dendritic cells, and T cells and decreased expression of PSGL-1 on B cells. PSGL-1 on monocytes from SSc patients failed to induce Syk phosphorylation or IL-10 production after interaction with P-selectin. Up to 60% of the IL-10–producing B cells expressed PSGL-1, pointing to a regulatory role for PSGL-1 in B cells, and PSGL-1+ B cells from SSc patients had decreased IL-10 production. ADAM8 expression was increased on antigen-presenting cells and T lymphocytes of SSc patients. Patients treated with calcium antagonists had lower levels of ADAM8 on APCs and T lymphocytes. Multivariate analysis indicated that the high percentage of ADAM8-expressing plasmacytoid dendritic cells discriminated patients from healthy donors. High PSGL-1 expression on dendritic cells was associated with the presence of interstitial lung disease.