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PERSPECTIVES FOR IMPROVEMENT OF THE THYMIC MICROENVIRONMENT THROUGH MANIPULATION OF THYMIC EPITHELIAL CELLS: A MINI-REVIEW
Imunossenescência
Células epiteliais tímicas
Circuitos intratímico
Células progenitoras epiteliais do timo
Expressão FoxN1
Thymic involution
Immune senescence
Thymic epithelial cells
Intrathymic circuitry
FoxN1 expression
Thymic epithelial progenitor cells
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Monash University. Department of Anatomy and Developmental Biology. Stem Cells and Immune Regeneration Laboratory. Melbourne, Vic., Australia.
Monash University. Department of Anatomy and Developmental Biology. Stem Cells and Immune Regeneration Laboratory. Melbourne, Vic., Australia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Monash University. Department of Anatomy and Developmental Biology. Stem Cells and Immune Regeneration Laboratory. Melbourne, Vic., Australia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Resumen en ingles
Thymic involution during aging is a major reason for the decreased
production of naive T cells and reduced immunity.
Alterations within the thymic microenvironment, characterized
by the loss of function of thymic epithelial cells (TECs)
and fibro-adipogenetic transformation, seem to underlie
this process, mainly through declining communication between
thymic stromal cells and developing thymocytes.
Specifically, the signaling mediated by cytokines and hormones
secreted by TECs declines during aging. Many therapies
based on the manipulation of growth factors and hormones
have succeeded in partially recovering the lymphoid
compartment and promoting thymic function. However,
considering that aging-induced thymic involution is multifactorial,
the thymic reestablishment achieved with treatments
that target isolated pathways is incomplete and transitory.
Here, we discuss the development of three novel approaches
for potentially sustained thymic recovery: the
induction of sustained forkhead box N1 expression, the activation
of endogenous thymic epithelial progenitor cells
(TEPCs), and the generation of TEPCs from pluripotent stem cells. Combined approaches targeting both TECs and lymphoid
cells will provide a potentially more effective strategy
for sustained rejuvenation of the thymus.
Palabras clave en portugues
Involução do TimoImunossenescência
Células epiteliais tímicas
Circuitos intratímico
Células progenitoras epiteliais do timo
Expressão FoxN1
Palabras clave en ingles
AgingThymic involution
Immune senescence
Thymic epithelial cells
Intrathymic circuitry
FoxN1 expression
Thymic epithelial progenitor cells
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