Targeted deletion of c‐Met in thymic epithelial cells leads to an autoimmune phenotype

Su, Min; Hu, Rong; Song, Yinhong; Lai, Laijun

doi:10.1111/imcb.1026

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…Although mature mTECs are also Aire + , a key role in promoting pGE in a wide array of tissue‐resistant antigens (TRAs), 2 no differences can be found in CD74‐deficient mice, indicating that CD74 deficiency does not affect Aire expression or Aire‐dependent TRAs (data not shown). Contrary to Su's report, 60 we have not found a predisposition to autoimmune disease in CD74‐deficient mice, suggesting that TRA expression is not drastically reduced as Aire + mTECs are less severely affected than the CD80 + MHCII + mTECs in CD74‐deficient mice. However, the percentages of Aire + , CD80 hi , Aire + CD80 hi , and Aire − CD80 hi mTECs have been reported to be strongly reduced in H2‐Aa −/− mice 30 .…”

Section: Discussioncontrasting

confidence: 99%

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF‐κB signaling pathway

Wang

Zhang

et al. 2021

FASEB j.

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Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self-tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs. However, the exact role of CD74 in regulating the development of mTEC is poorly defined. In this research, we found that loss of CD74 resulted in a significant diminution in the medulla, a selective reduction in the cell number of mature mTECs expressing CD80 molecules, which eventually led to impaired thymic CD4 + T cell development. Moreover, RNA-sequence analysis showed that CD74 deficiency obviously downregulated the canonical nuclear factor kappalight-chain-enhancer of activated B cells (NF-κB) signaling pathway in mTECs. Our results suggest that CD74 positively controls mTEC cellularity and maturation partially by activating the canonical NF-κB signaling pathway. K E Y W O R D SCD74 (invariant chain), maturation, medullary thymic epithelial cells (mTECs), NF-Κb, thymic epithelial cells (TECs) 2 of 15 | WANG et Al.

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Section: Discussioncontrasting

confidence: 99%

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF‐κB signaling pathway

Wang

Zhang

et al. 2021

FASEB j.

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“…Mesenchymal epithelial transition factor (c-Met) is expressed by TECs along with early T progenitors. The specific targeting of c-Met in TECs results in age-dependent progressive reduction in TECs number coupled with lower regulatory T cells (108). Similarly, the targeted loss of Shh in TECs reduces both cTEC and mTEC numbers (109).…”

Section: Epithelial Cell Control Of Thymopoiesismentioning

confidence: 99%

Thymus Functionality Needs More Than a Few TECs

Bhalla

Oers

2022

Front. Immunol.

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The thymus, a primary lymphoid organ, produces the T cells of the immune system. Originating from the 3rd pharyngeal pouch during embryogenesis, this organ functions throughout life. Yet, thymopoiesis can be transiently or permanently damaged contingent on the types of systemic stresses encountered. The thymus also undergoes a functional decline during aging, resulting in a progressive reduction in naïve T cell output. This atrophy is evidenced by a deteriorating thymic microenvironment, including, but not limited, epithelial-to-mesenchymal transitions, fibrosis and adipogenesis. An exploration of cellular changes in the thymus at various stages of life, including mouse models of in-born errors of immunity and with single cell RNA sequencing, is revealing an expanding number of distinct cell types influencing thymus functions. The thymus microenvironment, established through interactions between immature and mature thymocytes with thymus epithelial cells (TEC), is well known. Less well appreciated are the contributions of neural crest cell-derived mesenchymal cells, endothelial cells, diverse hematopoietic cell populations, adipocytes, and fibroblasts in the thymic microenvironment. In the current review, we will explore the contributions of the many stromal cell types participating in the formation, expansion, and contraction of the thymus under normal and pathophysiological processes. Such information will better inform approaches for restoring thymus functionality, including thymus organoid technologies, beneficial when an individuals’ own tissue is congenitally, clinically, or accidentally rendered non-functional.

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“…A c-Metspecific deficiency in TECs results in age-progressive reduction in TEC number and a reduced number of regulatory T cells. Consequently, c-Met TEC-conditional knockout mice displayed an autoimmune phenotype due to the severe infiltration of lymphocytes into multiple organs and increased activity of autoantibodies to peripheral tissue antigens (73). Thus, c-Met signaling in TECs is important for the maintenance of TECs and immune self-tolerance.…”

Section: Other Signaling Involved In Tec Developmentmentioning

confidence: 99%

Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development

et al. 2020

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The thymus is the primary lymphoid organ responsible for the generation and maturation of T cells. Thymic epithelial cells (TECs) account for the majority of thymic stromal components. They are further divided into cortical and medullary TECs based on their localization within the thymus and are involved in positive and negative selection, respectively. Establishment of self-tolerance in the thymus depends on promiscuous gene expression (pGE) of tissue-restricted antigens (TRAs) by TECs. Such pGE is co-controlled by the autoimmune regulator (Aire) and forebrain embryonic zinc fingerlike protein 2 (Fezf2). Over the past two decades, research has found that TECs contribute greatly to thymopoiesis and T cell development. In turn, signals from T cells regulate the differentiation and maturation of TECs. Several signaling pathways essential for the development and maturation of TECs have been discovered. New technology and animal models have provided important observations on TEC differentiation, development, and thymopoiesis. In this review, we will discuss recent advances in classification, development, and maintenance of TECs and mechanisms that control TEC functions during thymic involution and central tolerance.

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Targeted deletion of c‐Met in thymic epithelial cells leads to an autoimmune phenotype

Cited by 4 publications

References 30 publications

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF‐κB signaling pathway

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF‐κB signaling pathway

Thymus Functionality Needs More Than a Few TECs

Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development

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