Dendritic cell dynamics in sickle cell anemia and their impact on adaptive immunity

Author(s)

Matheus Ajeje de Souza

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2024-02-27

Examining board members

Renata Sesti Costa; Leonilda Maria Barbosa dos Santos; Bruno Deltreggia Benites

• Advisor: Renata Sesti Costa

Abstract

Dendritic cells (DCs) play a crucial role in both innate and adaptive immunity, acting as sentinels against pathogens and influencing the polarization of T lymphocytes towards specific profiles. In sickle cell anemia (SCA), a hemolytic disease, damage-associated molecules (DAMPs) such as hemoglobin and heme are released in large quantities during hemolysis, which can be recognized by monocytes, neutrophils and DCs, resulting in an inflammatory response chronic disease, a factor that contributes to the pathophysiology of SCA. Changes in the molecular patterns of antigen-presenting cells, such as DCs, can affect the balance in lymphocyte profiles, crucial in the defense against various diseases. Therefore, this study aims to investigate the phenotype of DC subpopulations regarding the profile of activation, migration and expression of hemeoxygenase 1 (HO-1), an enzyme that metabolizes heme, in SCA, correlating them with the response profile of T lymphocytes. Using an animal model of SCA, we observed an increase in DCs in lymph nodes and spleen, but a decrease in the bone marrow of sickle cell animals compared to healthy ones. Furthermore, there was a change in the percentages of different subtypes of DCs in sickle cell animals, as well as a reduction in their immediate progenitors in the bone marrow, indicating changes in the development and differentiation of DCs in SCA. Analysis of circulating DCs from patients revealed a decrease in some of these DC subpopulations with high HO-1 expression in the circulation. Taken together, these data indicate a possible change in the migration pattern. The associations between the parameters of dendritic cells (DCs), T lymphocytes and hematological data indicate a possible influence of DCs on clinical signs associated with the severity of SCA. Furthermore, they suggest that certain subtypes of DCs play a role in the polarization of T lymphocytes towards a Th17 profile, recognized by their inflammatory character, in addition to suggesting that iDCs may be related to the reduction of Treg lymphocytes in patients, which may contribute to the chronic inflammation in SCA. The study highlights the dynamics of CDs in SCA and highlights the continued need for research to develop specific therapeutic strategies that contribute to patients' quality of life (AU)

• FAPESP's process: 22/01755-4 - Mechanisms involved in activation of dendritic cells and monocytes upon sickle cell anemia
• Grantee: Matheus Ajeje de Souza
• Support Opportunities: Scholarships in Brazil - Master