Role of DCs in IFN-I production in sickle cell anemia, their function in chronic inflammation and possible development of autoimmune diseases

• Grant number: 21/14728-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Renata Sesti Costa
• Grantee: Izabela Felice Paes
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/09704-7 - Dendritic cells in Sickle Cell Anemia: molecular mechanisms involved in regulating inflammation and adaptive immune response, AP.JP

Abstract

Sickle cell anemia (SCA) is one of the most common hemoglobinopathies around the world. Patients affected by SCA have a reduced quality of life due to complications resulting from changes in the shape and physical properties of erythrocytes. These complications consist of chronic hemolytic anemia, pain crises, organ dysfunction, susceptibility to infections, among others. It is also known that genes induced by IFN-I are among the most expressed genes in mononuclear cells from blood of patients with SCA, but there is no report on the role of IFN-I or plasmacytoid DCs, the main producers of this cytokine, in the pathology of the disease. Our preliminary data show that patients with SCA have a higher amount and proportion of total blood DCs than healthy individuals. Among these cells, there is an increase in the proportion of pre-DCs and a reduction in circulating cDCs1, which indicates higher generation of DCs in the bone marrow and suggests differential activation and migration between DC subsets during the inflammatory process of SCA. In the present work, we intend to investigate the role of IFN-I in the pathology of SCA and its susceptibility to autoimmune disease, in addition to unraveling whether DCs, or subpopulations of these cells, are the sources of IFN-I in the disease. We hope that the data will reveal more information about the establishment of the chronic inflammatory state and the immune dysfunction presented by patients with SCA and that they will expose new therapeutic targets for specific regulation of the pathology.