DISTRIBUTION, ACTIVATION, AND DEVELOPMENT OF DENDRITIC CELLS SUBSETS UPON SICKLE CELL DISEASE

Matheus Ajeje de Souza; Izabela Felice Paes; Marina Borges Dorigatti; Fernando Ferreira Costa; Dra. Renata Sesti Costa

Todos os Trabalhos

Trabalho

Título do Trabalho

DISTRIBUTION, ACTIVATION, AND DEVELOPMENT OF DENDRITIC CELLS SUBSETS UPON SICKLE CELL DISEASE

Autores

Matheus Ajeje de Souza
Izabela Felice Paes
Marina Borges Dorigatti
Fernando Ferreira Costa
Dra. Renata Sesti Costa

Modalidade

Apresentação de Pôster

Área temática

Imunologia

Data de Publicação

09/06/2023

País da Publicação

Brasil

Idioma da Publicação

Inglês

Página do Trabalho

https://www.even3.com.br/anais/v-gbmeeting/609214-distribution-activation-and-development-of-dendritic-cells-subsets-upon-sickle-cell-disease

ISBN

978-85-5722-785-9

Palavras-Chave

Dendritic Cells, Sickle Cell Disease

Resumo

Sickle Cell Disease (SCD) is one of the most common hemoglobinopathies in the world. A point mutation in the sixth codon of the gene that encodes beta globin causes a substitution of amino acid and forms an anomalous hemoglobin called hemoglobin S, which polymerizes during their deoxygenation cycles. Thereby, the red blood cells assume the sickled form, weakening its structure, becoming more prone to rupture. Molecules released in hemolysis, such as heme and hemoglobin, are recognized as damage-associated molecular patterns (DAMPs) by dendritic cells (DCs) and monocytes that trigger an inflammatory response and cause oxidative stress. Patients with SCD show an alteration in dendritic cell phenotypes. Such alteration may affect the polarization of the patient's adaptive immune response, since DCs are the main modulators of the lymphocyte profile through contact and cytokines-dependent manners. In this study, we intend to further characterize the subpopulations of DCs during sickle cell disease. For this, homozygous Townes (SS) female transgenic mice (SCD model) and Townes wild type littermates (AA) (control group) were used for phenotyping of DCs and DCs progenitors from peripheral lymph nodes, spleen and bone marrow using flow cytometry. In vitro DCs differentiation was performed by incubating bone marrow cells with flt3l for 9 days. SCD animals (SS) showed a decrease in the percentage of total DCs in the spleen and bone marrow when compared to the control group (AA), whereas the absolute number of total DCs in the lymph nodes of SS mice increased, which may indicate a greater migration of these cells to peripheral lymph nodes. Regarding the proportion of DC subpopulations, there was a significant increase in the percentage of conventional type 1 dendritic cells (cDC1s) in all organs of SCD animals, whereas the relative percentage of pDCs was significantly lower in the bone marrow, indicating a change in the development or death of subpopulations of DCs during SCD. Furthermore, pDCs from SS mice showed a more mature phenotype in the three organs analyzed, as observed by a significant increase in Sca-1 expression. On the other hand, both cDC1 and cDC2 from SS mice showed a more immature profile as observed by lower MHC-II and CD86 expression. Analysis of monocytes and DCs progenitors (MDP), which are Lin-CD135+CD117+CD115+, and the immediate common DCs progenitors (CDP), which are Lin-CD135+CD117-CD115+, showed that there is an accumulation on MDPs and a drop on CDPs within bone marrow from SS mice, which shows an alteration on DCs compartment in SS mice since their development stage. In vitro differentiation of DCs from bone marrow cells revealed that all three main DCs subsets are differentiated from SS mice cells in a similar manner than controls, indicating that the change in DCs development in SS mice is due to the environment instead of to a DC or DC progenitor intrinsic defect. These data may help us understand the behavior of dendritic cells during SCD, both in terms of the proportion/distribution of their subtypes and their influence on the inflammatory picture of the disease. Financial support: FAPESP

Título do Evento: V GBMeeting
Cidade do Evento: Campinas
Título dos Anais do Evento: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP
Nome da Editora: Even3
Meio de Divulgação: Meio Digital

Como citar

SOUZA, Matheus Ajeje de et al.. DISTRIBUTION, ACTIVATION, AND DEVELOPMENT OF DENDRITIC CELLS SUBSETS UPON SICKLE CELL DISEASE.. In: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP. Anais...Campinas(SP) Unicamp, 2023. Disponível em: https//www.even3.com.br/anais/v-gbmeeting/609214-DISTRIBUTION-ACTIVATION-AND-DEVELOPMENT-OF-DENDRITIC-CELLS-SUBSETS-UPON-SICKLE-CELL-DISEASE. Acesso em: 03/01/2025