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Front. Immunol. | doi: 10.3389/fimmu.2019.01268

Thrombospondin-1/CD47 Interaction Regulates Th17 and Treg Differentiation in Psoriasis

 Pedro Rodríguez-Jiménez1,  Pablo Chicharro1,  Mar L. Velasco1,  Danay Cibrian Vera1, 2,  Laura Trigo Torres3,  Alicia Vara3, María J. Calzada4, Francisco Sánchez Madrid2, 3, 5,  Hortensia De La Fuente Flores2, 3* and Esteban Dauden1*
  • 1Dermatology Service, Hospital of the Princess, Spain
  • 2Institute of Health Research of the University Hospital of La Princesa, Spain
  • 3Servicio de Inmunología, Hospital de la Princesa, Spain
  • 4Autonomous University of Madrid, Spain
  • 5Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain

Accumulating evidence on the role of Thrombospondin-1 (TSP-1) in the immune response has emerged during the last years. In spite of the importance of TSP-1 not only as anti-angiogenic factor but also as an immunomodulatory molecule, studies on the role of TSP-1 in psoriasis have been neglected. TSP-1 and CD47 expression were analyzed in skin samples from psoriasis patients and control subjects using RT-PCR and immunofluorescence. Expression of these molecules was also evaluated in peripheral blood CD4+ T cells, moDCs and circulating primary DCs. The functional role of TSP-1/CD47 signaling axis in psoriasis was assessed in Th17 and Treg differentiation assays. Additionally, small interfering RNA assays specific to TSP-1 were performed in CD4+ T cells and monocyte derived DC to specifically evaluate the function of this protein. Lesional skin of psoriasis patients expressed lower TSP-1 and CD47 mRNA levels compared to non-lesional skin or skin from controls. Immunofluorescence staining revealed decreased expression of CD47 in CD45+ dermal cells from psoriasis samples compared to control subjects. Peripheral CD4+ T cells and circulating primary DCs from psoriasis also expressed lower levels of CD47 compared to controls. Although no significant differences were detected in TSP-1 expression in CD4+ T cells and moDCs between patients and controls, TSP-1 expression in psoriasis patients inversely correlated with disease activity evaluated by the Psoriasis Area and Index Activity. Furthermore, exogenous TSP-1 inhibited Th17 differentiation and stimulated the differentiation of CD4+ T cells towards Treg cells. Furthermore, RNA interference specific for TSP-1 confirmed the role of this molecule as a negative regulator of T cell activation. Because of the impact of TSP-1/CD47 signaling axis in Th17 and Treg differentiation, a dysregulated expression of these molecules in the immune cells from psoriasis patients may favor the exacerbated inflammatory response in this disease.

Keywords: TSP-1, Th17, Treg, Psoriasis, cd47

Received: 25 Jan 2019; Accepted: 17 May 2019.

Edited by:

J. Michelle Kahlenberg, Michigan Medicine, University of Michigan, United States

Reviewed by:

Thomas S. McCormick, Case Western Reserve University, United States
David D. Roberts, National Institutes of Health (NIH), United States  

Copyright: © 2019 Rodríguez-Jiménez, Chicharro, Velasco, Cibrian Vera, Trigo Torres, Vara, Calzada, Sánchez Madrid, De La Fuente Flores and Dauden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Hortensia De La Fuente Flores, Servicio de Inmunología, Hospital de la Princesa, Madrid, Madrid, Spain, hortensia.fuente@salud.madrid.org
Dr. Esteban Dauden, Dermatology Service, Hospital of the Princess, Madrid, Spain, estebandauden@medynet.com