Thymus Ontogeny and Development

Múñoz, Juan José; González, Antonio Uriarte

doi:10.1007/978-3-030-12040-5_2

Cited by 8 publications

(15 citation statements)

References 94 publications

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“…As mentioned above, TE derives from the endoderm of the 3rd pharyngeal pouch [ 4 ]. In this early thymic primordium, a common bipotent thymic progenitor cell was identified capable of giving rise to both committed cTEC precursors and mTE progenitor cells [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Thymic Epithelium Is Originated From Epithelial Progenitomentioning

confidence: 99%

“…The thymus is a primary lymphoid organ derived from the endoderm of the 3rd pharyngeal pouch implicated in the maturation of thymocytes and, therefore, key for establishing the immune surveillance. This organ does not contain self-renewing lymphoid precursor cells and therefore, is colonized by lymphoid precursors coming either from the fetal liver through mesenchyme or from the adult bone marrow via the blood vessels [ 4 ]. Within the thymus, the developing thymocytes move throughout a 3D thymic epithelial (TE) network, interacting with the thymic epithelial cells (TECs) of two histologically different compartments: the cortex and the medulla [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

García‐Ceca

Montero-Herradón

Zapata

2020

Cells

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Intimate interactions between thymic epithelial cells (TECs) and thymocytes (T) have been repeatedly reported as essential for performing intrathymic T-cell education. Nevertheless, it has been described that animals exhibiting defects in these interactions were capable of a proper positive and negative T-cell selection. In the current review, we first examined distinct types of TECs and their possible role in the immune surveillance. However, EphB-deficient thymi that exhibit profound thymic epithelial (TE) alterations do not exhibit important immunological defects. Eph and their ligands, the ephrins, are implicated in cell attachment/detachment and govern, therefore, TEC–T interactions. On this basis, we hypothesized that a few normal TE areas could be enough for a proper phenotypical and functional maturation of T lymphocytes. Then, we evaluated in vivo how many TECs would be necessary for supporting a normal T-cell differentiation, concluding that a significantly low number of TEC are still capable of supporting normal T lymphocyte maturation, whereas with fewer numbers, T-cell maturation is not possible.

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Section: Thymic Epithelium Is Originated From Epithelial Progenitomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

García‐Ceca

Montero-Herradón

Zapata

2020

Cells

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“…The expression of Gcm2 and Foxn1 is maintained throughout the development of the organs and after birth, both in mammals and birds [ 24 , 25 , 49 ]. Increasing evidence has been produced in recent years showing the fine-tuning of Foxn1 levels in the regulation of several processes, such as thymic epithelium differentiation, adult thymus homeostasis, and thymic involution (reviewed in [ 50 ]). Thymic Epithelial Marker—Foxn1 …”

Section: Embryonic Origin Of the Thymusmentioning

confidence: 99%

Thymus Inception: Molecular Network in the Early Stages of Thymus Organogenesis

Figueiredo

Zilhão

Neves

2020

IJMS

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The thymus generates central immune tolerance by producing self-restricted and self-tolerant T-cells as a result of interactions between the developing thymocytes and the stromal microenvironment, mainly formed by the thymic epithelial cells. The thymic epithelium derives from the endoderm of the pharyngeal pouches, embryonic structures that rely on environmental cues from the surrounding mesenchyme for its development. Here, we review the most recent advances in our understanding of the molecular mechanisms involved in early thymic organogenesis at stages preceding the expression of the transcription factor Foxn1, the early marker of thymic epithelial cells identity. Foxn1-independent developmental stages, such as the specification of the pharyngeal endoderm, patterning of the pouches, and thymus fate commitment are discussed, with a special focus on epithelial–mesenchymal interactions.

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“…The three-dimensional (3D) structure of the thymus is composed of two histologically distinct but closely related compartments. The cortex is mainly formed by cortical thymic epithelial cells (cTECs), and the medulla is primarily formed by medullary thymic epithelial cells (mTECs), which in mice present the CD45 - , EpCam + , Ly51 + , UEA1 + phenotype [1-3]. Other cell types include thymic seeding progenitors, thymocytes at different stages of maturation, including double-negative (CD4 - CD8 - ), double-positive (CD4 + CD8 + ), and single-positive (CD4 + CD8 - and CD4 - CD8 + ) thymocytes, thymic B cells, macrophages, dendritic cells, and Hassall’s corpuscles [2].…”

Section: Introductionmentioning

confidence: 99%

The absence of the autoimmune regulator gene (AIRE) impairs the three-dimensional structure of medullary thymic epithelial cell spheroids

Monteleone-Cassiano

Dernowsek

Mascarenhas

et al. 2021

Preprint

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Besides controlling the expression of peripheral tissue antigens, the autoimmune regulator (AIRE) gene also regulates the expression of adhesion genes in medullary thymic epithelial cells (mTECs), an essential process for mTEC-thymocyte interaction for triggering the negative selection in the thymus. For these processes to occur, it is necessary that the medulla compartment forms an adequate three-dimensional (3D) architecture, preserving the thymic medulla. Previous studies have shown that AIRE knockout (KO) mice have a small and disorganized thymic medulla; however, whether Aire influences the mTEC-mTEC interaction in the maintenance of the 3D structure has been little explored. Considering that AIRE controls cell adhesion genes, we hypothesized that this gene affects 3D mTEC-mTEC interaction. To test this, we constructed an in vitro model system for mTEC spheroid formation, in which cells adhere to each other, establishing a 3D structure. The effect of Aire on mTEC-mTEC adhesion was evaluated by comparing AIRE wild type (AIREWT) versus Aire KO (AIRE-/-) mTECs. Considering the 3D spheroid model evaluated, we reported that the absence of AIRE disorganizes the 3D structure of mTEC spheroids, promotes a differential regulation of mTEC classical surface markers, and modulates genes encoding adhesion and other molecules.

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Thymus Ontogeny and Development

Cited by 8 publications

References 94 publications

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

Thymus Inception: Molecular Network in the Early Stages of Thymus Organogenesis

The absence of the autoimmune regulator gene (AIRE) impairs the three-dimensional structure of medullary thymic epithelial cell spheroids

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