Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis

Wu, Hao; Li, Xiaohan; Zhou, Chen; Yu, Qing; Ge, Shiyao; Pan, Zihui; Zhao, Yangjing; Sheng, Xia; Zhou, Xiaoming; Liu, Xia; Wang, Hui; Shao, Qixiang

doi:10.1038/s41420-021-00619-5

Cited by 8 publications

(3 citation statements)

References 47 publications

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“…Since S1 contains the receptor binding domain of the spike protein, it could bind to the ACE2 receptors on mTECs, inducing a damaging inflammatory effect, as has been demonstrated for endothelial cells [69]. Even independently of the spike protein, returning DCs have been shown to directly inhibit TEC proliferation and induce their apoptosis by activating the Jagged1/Notch3 signalling pathway [95].…”

Section: Potential For Damage To the Thymic Epithelium And Accelerate...mentioning

confidence: 96%

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

Kyriakopoulos,

Nigh,

McCullough

et al. 2024

Preprint

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When an antigen stimulates the immune system, specific T regulatory (Treg) and T effector (Teff) subpopulations develop from naïve T cells. The Treg cell population will produce the memory Treg (mTreg) cells against that specific antigen. An inappropriate homeostatic balance among Teff, Treg and mTreg cells can direct the immune system toward either cancer or autoimmunity. When cancer is present, Treg cells suppress anti-tumor immunity, and, when cancer is absent, Treg cells play the beneficial role of preventing the development of autoimmunity. In this review, we analyze Treg responses after SARS-CoV-2 mRNA vaccination and find distinct pathological responses under differing conditions. In cancer patients, the degree of disease progression depends on the cancer status at the time of vaccination and the type of cancer treatment they receive concurrently. We hypothesize that migration of circulating dendritic cells and mTreg cells back to the thymus accelerates thymic involution, a direct cause of immunosenescence. In summary, the Treg responses produced after mRNA vaccination and the subsequent mRNA-encoded SARS-CoV-2 spike protein expression may lead to a harmful influence on the immune system of vaccinees, and subsequent accelerated development of cancer and autoimmune disease. These mechanisms are consistent with both epidemiological findings and case reports.

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Section: Potential For Damage To the Thymic Epithelium And Accelerate...mentioning

confidence: 96%

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

Kyriakopoulos,

Nigh,

McCullough

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…APCs, like dendritic cells (DCs), are efficient immune forerunners. [ 114,115 ] Apart from limiting T cell proliferation, the immunosuppressive tumor milieu reduces DC migration, stimulation, and antigen presentation. [ 44,111 ] Researchers have been striving to develop artificial APCs (aAPCs) as a substitute for innate APCs for the past 20 years.…”

Section: Nanoparticles/drug Hitchhiking Tactics On Immune Cells For C...mentioning

confidence: 99%

The Role of Hitchhiking in Cancer Therapeutics—A Review

Padmakumar

Koyande

Rengan

2022

Advanced Therapeutics

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Hitchhiking is a phenomenon of cruising on surfaces. Inspired by this process, biomimetic delivery systems leveraging the intrinsic ability of circulatory cells to target tumors exhibit considerable potential in cancer theranostics. Besides human circulatory cell‐mediated hitchhiking, bacteria‐driven hitchhiking strategies also manifest promise in cancer therapy. Such tactics are primarily built using nonpathogenic invasive bacteria with tumor homing capabilities. The chemotherapeutic cargos are hitchhiked onto the circulatory cells or bacterial spores for tumor‐targeted delivery. By integrating the benefits of such cells and therapeutic cargo, numerous efficient delivery systems that implement the notion of hitchhiking for cancer therapy are generated. Following an overview of several hitchhiking concepts, this article reviews various cellular and bacterial hitchhiking approaches for cancer treatment. Additionally, the challenges and prospects in the field of cancer theranostics related to hitchhiking are also discussed.

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“…Since a majority of thymic DCs come from the periphery, whether migratory DCs play a role in thymus damage post infection was unclear. A recent publication by Haojie Wu et al showed that mature DCs from the circulation can enter the thymus and induce thymus involution through the Notch signaling pathway (47). Upon activation by antigens such as lipopolysaccharide and ovalbumin, DCs have been shown to enhance Jagged1 expression (48,49).…”

Section: Thymic Dendritic Cells In Post Infectionmentioning

confidence: 99%

Thymic Microenvironment: Interactions Between Innate Immune Cells and Developing Thymocytes

Wang

Zúñiga‐Pflücker

2022

Front. Immunol.

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The thymus is a crucial organ for the development of T cells. T cell progenitors first migrate from the bone marrow into the thymus. During the journey to become a mature T cell, progenitors require interactions with many different cell types within the thymic microenvironment, such as stromal cells, which include epithelial, mesenchymal and other non-T-lineage immune cells. There are two crucial decision steps that are required for generating mature T cells: positive and negative selection. Each of these two processes needs to be performed efficiently to produce functional MHC-restricted T cells, while simultaneously restricting the production of auto-reactive T cells. In each step, there are various cell types that are required for the process to be carried out suitably, such as scavengers to clean up apoptotic thymocytes that fail positive or negative selection, and antigen presenting cells to display self-antigens during positive and negative selection. In this review, we will focus on thymic non-T-lineage immune cells, particularly dendritic cells and macrophages, and the role they play in positive and negative selection. We will also examine recent advances in the understanding of their participation in thymus homeostasis and T cell development. This review will provide a perspective on how the thymic microenvironment contributes to thymocyte differentiation and T cell maturation.

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Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis

Cited by 8 publications

References 47 publications

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

The Role of Hitchhiking in Cancer Therapeutics—A Review

Thymic Microenvironment: Interactions Between Innate Immune Cells and Developing Thymocytes

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