Role of SCARF1 in Efferocytosis and Prevention of Lupus

Abstract

We demonstrated that the scavenger receptor SCARF1 (Scavenger Receptor Class F member 1) is a non-redundant AC receptor[1]. Mice with global Scarf1 deficiency spontaneously develop autoimmune disease with clinical manifestations that are strikingly similar to human SLE. Our publication and supporting data provide ample support for the hypothesis that SCARF1 engulfs and clears ACs to prevent loss of tolerance, inflammation, and spontaneous development of autoimmunity. Therefore, we hypothesize that SCARF1 plays an important role in the physiological clearance of apoptotic debris, and that dysregulated or loss of SCARF1 expression on cells leads to impaired AC uptake, loss of self-tolerance, and development of SLE. During the 10/22-9/23 cycle we identify an increased in soluble SCARF1 on SLE patients when compared to controls. Suggesting that part of the dysregulation could be mediated by cleavage of SCARF1 from cells. Furthermore, in our mouse models we performed some chimeras to characterize the role of SCARF1 in hematopoietic vs non-hematopoietic cells in the development of autoimmunity. Our data shows that both groups of cells are essential; however, hematopoietic cells are necessary in the initiation of disease. Non-hematopoietic cells are needed for the maintenance. While out data suggest a non-redundant role for SCARF1 in the initiation and maintenance of autoimmunity, additional work is needed to dissect the specific role of the receptor. For 10/23-9/24 our lab efforts will investigate the relation on soluble SCARF1 and autoantibodies, identify if SCARF1 autoantibodies are pathogenic and how N-modifications affect their role.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2023
Accession Number
AD1225062

Entities

People

  • Zaida G. Ramirez-ortiz

Organizations

  • University of Massachusetts Medical School

Tags

Fields of Study

  • Medicine

Readers

  • Clinical Trial Research.
  • Immunology
  • Immunology and Pathology