Publicação
Unveil the role of LAMP2 in T cell development in the thymus
| Resumo: | The development of immunocompetent T cells is fundamental for maintaining normal physiological functions. This process is facilitated by an inductive microenvironment formed by thymic epithelial cells (TECs) within the thymus, which play a critical role in both T cell selection and the induction of immune tolerance. Additionally, TECs have the capacity to process and express unique sets of self-peptide-MHC complexes, whose formation depends on specialized proteolytic machinery. Previous studies from our group have demonstrated that LAMP2 (lysosome-associated membrane protein 2) acts as an important regulator in the thymic stroma, specifically in the development of CD4 T cells (Rodrigues et al., 2023). The primary objective of this dissertation was to elucidate the role of LAMP2 in TECs in regulating T cell development, particularly its influence on positive and negative selection during the thymic maturation of CD4⁺ cells. To achieve this objective, it was developed a murine model with specific deletion of the LAMP2 gene in TECs. The results obtained indicate that LAMP2 ablation in TECs leads to a reduced population of CD4⁺ T cells completing positive selection. Furthermore, the absence of LAMP2 was associated with a decrease in the capacity for MHC-II processing, suggesting a critical role for this protein in maintaining the functionality of the thymic microenvironment. These findings contribute to the advancement of knowledge regarding thymic biology and its molecular interactions, highlighting the relevance of LAMP2 in regulating T cell development, and offering new perspectives for the development of therapeutic interventions in immune-related diseases. |
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| Autores principais: | Alves, Ana Carolina Brito de Farias Hage |
| Assunto: | Thymus Thymic selection CD4⁺ LAMP2 |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | The development of immunocompetent T cells is fundamental for maintaining normal physiological functions. This process is facilitated by an inductive microenvironment formed by thymic epithelial cells (TECs) within the thymus, which play a critical role in both T cell selection and the induction of immune tolerance. Additionally, TECs have the capacity to process and express unique sets of self-peptide-MHC complexes, whose formation depends on specialized proteolytic machinery. Previous studies from our group have demonstrated that LAMP2 (lysosome-associated membrane protein 2) acts as an important regulator in the thymic stroma, specifically in the development of CD4 T cells (Rodrigues et al., 2023). The primary objective of this dissertation was to elucidate the role of LAMP2 in TECs in regulating T cell development, particularly its influence on positive and negative selection during the thymic maturation of CD4⁺ cells. To achieve this objective, it was developed a murine model with specific deletion of the LAMP2 gene in TECs. The results obtained indicate that LAMP2 ablation in TECs leads to a reduced population of CD4⁺ T cells completing positive selection. Furthermore, the absence of LAMP2 was associated with a decrease in the capacity for MHC-II processing, suggesting a critical role for this protein in maintaining the functionality of the thymic microenvironment. These findings contribute to the advancement of knowledge regarding thymic biology and its molecular interactions, highlighting the relevance of LAMP2 in regulating T cell development, and offering new perspectives for the development of therapeutic interventions in immune-related diseases. |
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