Thymic epithelial cell heterogeneity: TEC by TEC

Kadouri, Noam; Nevo, Shir; Goldfarb, Yael; Abramson, Jakub

doi:10.1038/s41577-019-0238-0

Cited by 127 publications

(174 citation statements)

References 123 publications

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“…Recently, single cell-RNA sequencing analysis [ 24 ] confirmed that most embryonic TECs show a strong cTEC footprint. According to this model, TEPCs would be committed to the cortical epithelial cell lineage by default, whereas the differentiation into mTECs would require the activation of a medullary specific transcriptional program together with the downregulation of cTEC committed genes [ 10 ].…”

Section: Thymic Epithelium Is Originated From Epithelial Progenitomentioning

confidence: 99%

“…Increasing evidence supports that mTEC differentiation continues beyond the Aire + stages of thymic epithelium development, to give rise to the so-called tuft cells as well as to terminally differentiated epithelial cells that form a part of the named Hassall’s bodies (or corpuscles) [ 57 , 90 , 91 ]. These terminal epithelial cells express numerous markers of differentiated keratinocytes of the outer epidermal layers, such as keratin 1, keratin 10, involucrins, desmogleins, and Serine protease inhibitor Kazal type 5 (SPINK5) [ 10 ]. Whether Aire governs or not this final differentiation of mTECs is a matter of discussion [ 10 ].…”

Section: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

“…These terminal epithelial cells express numerous markers of differentiated keratinocytes of the outer epidermal layers, such as keratin 1, keratin 10, involucrins, desmogleins, and Serine protease inhibitor Kazal type 5 (SPINK5) [ 10 ]. Whether Aire governs or not this final differentiation of mTECs is a matter of discussion [ 10 ]. In addition, the functions of these terminal mTECs are controversial.…”

Section: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

“…Mucosal tuft cells produce IL25 and express genes involved in the synthesis of acetylcholine, prostaglandins, or leukotrienes, and in the signaling of taste reception, such as Phospholypase C beta 2 (Plcb2), Transient receptor potential channel subfamily 5 (Trpm5), G protein subunit beta 3 (Gnb3), and G protein subunit gamma 13 (Gng13). Thymic tuft cells also express several members of the taste receptor 2 family as well as L1CAM, DLCK1, MHCII, and CD74, but not other genes characteristic of mucosal tuft cells (i.e., Galectins 2 and 4 (Lgals 2 and Lgals4), Mucin13, Fatty acid binding protein 1 (Fabp1), and Apolipoprotein A1 (Apoa1)) [ 10 ].…”

Section: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

“…Positively selected SP thymocytes up-regulate the expression of CCR7 and migrate into the medulla through the cortico-medullary junction to interact with medullary (m) TECs that express ligands of CCR7 (i.e., CCL19, CCL21) [ 7 ]. mTECs have the capacity to present peptides derived from tissue proteins (TSA, tissue specific antigens) expressed outside the thymus with the concourse of, at least, two different transcription factors: Autoimmune regulator (Aire) [ 5 , 8 , 9 , 10 , 11 ] and Forebrain embryonic Zn-finger-like (Fefz2) [ 12 ]. These mTEC–thymocyte interactions are essential for the induction of thymic selection, as thymocytes whose TCRαβ recognize with high-affinity TSA are eliminated by apoptosis (negative selection) [ 5 , 10 ] or differentiate to Treg cells [ 3 ].…”

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: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

Section: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

Section: Mtecs Constitute a Heterogeneous Thymic Cell Population Imentioning

confidence: 99%

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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Thymus Extracellular Matrix‐Derived Scaffolds Support Graft‐Resident Thymopoiesis and Long‐Term In Vitro Culture of Adult Thymic Epithelial Cells

Asnaghi

Barthlott

Gullotta

et al. 2021

Adv Funct Materials

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The thymus provides the physiological microenvironment critical for the development of T lymphocytes, the cells that orchestrate the adaptive immune system to generate an antigen‐specific response. A diverse population of stroma cells provides surface‐bound and soluble molecules that orchestrate the intrathymic maturation and selection of developing T cells. Forming an intricate 3D architecture, thymic epithelial cells (TEC) represent the most abundant and important constituent of the thymic stroma. Effective models for in and ex vivo use of adult TEC are still wanting, limiting the engineering of functional thymic organoids and the understanding of the development of a competent immune system. Here a 3D scaffold is developed based on decellularized thymic tissue capable of supporting in vitro and in vivo thymopoiesis by both fetal and adult TEC. For the first time, direct evidences of feasibility for sustained graft‐resident T‐cell development using adult TEC as input are provided. Moreover, the scaffold supports prolonged in vitro culture of adult TEC, with a retained expression of the master regulator Foxn1. The success of engineering a thymic scaffold that sustains adult TEC function provides unprecedented opportunities to investigate thymus development and physiology and to design and implement novel strategies for thymus replacement therapies.

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Recent Advancements in Regenerative Approaches for Thymus Rejuvenation

Sharma

Moroni

2021

Advanced Science

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The thymus plays a key role in adaptive immunity by generating a diverse population of T cells that defend the body against pathogens. Various factors from disease and toxic insults contribute to the degeneration of the thymus resulting in a fewer output of T cells. Consequently, the body is prone to a wide host of diseases and infections. In this review, first, the relevance of the thymus is discussed, followed by thymic embryological organogenesis and anatomy as well as the development and functionality of T cells. Attempts to regenerate the thymus include in vitro methods, such as forming thymic organoids aided by biofabrication techniques that are transplantable. Ex vivo methods that have shown promise in enhancing thymic regeneration are also discussed. Current regenerative technologies have not yet matched the complexity and functionality of the thymus. Therefore, emerging techniques that have shown promise and the challenges that lie ahead are explored.

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Thymic epithelial cell heterogeneity: TEC by TEC

Cited by 127 publications

References 123 publications

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

Thymus Extracellular Matrix‐Derived Scaffolds Support Graft‐Resident Thymopoiesis and Long‐Term In Vitro Culture of Adult Thymic Epithelial Cells

Recent Advancements in Regenerative Approaches for Thymus Rejuvenation

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