Research Topic

Thymus Function and Aging: A Focus on Thymic Epithelial Cells

About this Research Topic

The recent COVID pandemic pointed out once more the enormous importance of the immune system for the survival of our species. Since the discovery of the thymus function in the late sixties by Professor Miller and the studies of its role in T cell development, differentiation, and selection till the present day, our understanding of the immune system has broadened. Lymphocytes carry out the multiple tasks of fighting pathogens as well as keeping the organism healthy. Entering the thymus, precursor lymphocytes interact with the thymus stromal compartment mainly built of epithelial cells, and from the enormous variety of produced lymphocytes, only the specific ones can survive a rigorous checkpoint control and selection. Thymus aging begins already after puberty and initiates a decline of immune function, which is associated with tumors, infectious or autoimmune diseases.

Major groups have described epithelial stem cells in the thymus, a previously unidentified subpopulation defined as EpCam+UEA1-Ly-51+PLET1+ which contains bipotent thymus epithelial cell (TEC) progenitors or the α6-integrinhi Sca-1hi postnatal bipotent TEC thymus subpopulation. It is still not resolved the nature of the epithelial stem cells and if the 3D cultures from Foxn1− thymic precursors or from Foxn1− EpCAM− mesenchymal cells have the potential to generate epithelial cells or only adipocytes. Still, these mesenchymal cells might be important to the maintenance of the thymic microenvironment through delivering growth factors to the developing TEC and cytokines to lymphocyte precursors. Most of the described adult stem cells have been studied in mice but there is much less evidence regarding human thymus development and aging. Another interesting aspect is the regeneration of the thymus by only partial thymectomy preceding cardiac surgery or regeneration in vivo by administration of interleukin 22 or BMP4 or small chemical compounds.

This Research Topic welcomes Original Research, Reviews, Systematic Review, Methods, Mini Review, Hypothesis and Theory, Perspective papers, Clinical Trials, Case Report, Classification, and Technology and Code articles that address, but are not limited to, the following topics:

• Thymic epithelial cell development and aging impact on lymphocyte output and on thymus function modification

• Regeneration of thymus function to promote the development of T lymphocyte-based therapeutics;

• Tools for thymus renewal in vitro or in vivo, either from the mouse or human tissues;

• Phylogenetic development of the thymus from lampreys to chicken and mammals;

• New methods for isolating and culturing of thymus epithelial cells, dendritic, mesenchymal, and endothelial cells, their function and involvement in proper thymus function;

• Studies on small chemical compounds, transcription factors, microRNAs, proteins, and interleukins which influence the thymic function, involution, or regeneration;

• Reversibility of the thymus aging.


Keywords: Thymus, development, T lymphocytes, adult stem cells, epithelial cells, aging, FoxN1, NOTCH


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The recent COVID pandemic pointed out once more the enormous importance of the immune system for the survival of our species. Since the discovery of the thymus function in the late sixties by Professor Miller and the studies of its role in T cell development, differentiation, and selection till the present day, our understanding of the immune system has broadened. Lymphocytes carry out the multiple tasks of fighting pathogens as well as keeping the organism healthy. Entering the thymus, precursor lymphocytes interact with the thymus stromal compartment mainly built of epithelial cells, and from the enormous variety of produced lymphocytes, only the specific ones can survive a rigorous checkpoint control and selection. Thymus aging begins already after puberty and initiates a decline of immune function, which is associated with tumors, infectious or autoimmune diseases.

Major groups have described epithelial stem cells in the thymus, a previously unidentified subpopulation defined as EpCam+UEA1-Ly-51+PLET1+ which contains bipotent thymus epithelial cell (TEC) progenitors or the α6-integrinhi Sca-1hi postnatal bipotent TEC thymus subpopulation. It is still not resolved the nature of the epithelial stem cells and if the 3D cultures from Foxn1− thymic precursors or from Foxn1− EpCAM− mesenchymal cells have the potential to generate epithelial cells or only adipocytes. Still, these mesenchymal cells might be important to the maintenance of the thymic microenvironment through delivering growth factors to the developing TEC and cytokines to lymphocyte precursors. Most of the described adult stem cells have been studied in mice but there is much less evidence regarding human thymus development and aging. Another interesting aspect is the regeneration of the thymus by only partial thymectomy preceding cardiac surgery or regeneration in vivo by administration of interleukin 22 or BMP4 or small chemical compounds.

This Research Topic welcomes Original Research, Reviews, Systematic Review, Methods, Mini Review, Hypothesis and Theory, Perspective papers, Clinical Trials, Case Report, Classification, and Technology and Code articles that address, but are not limited to, the following topics:

• Thymic epithelial cell development and aging impact on lymphocyte output and on thymus function modification

• Regeneration of thymus function to promote the development of T lymphocyte-based therapeutics;

• Tools for thymus renewal in vitro or in vivo, either from the mouse or human tissues;

• Phylogenetic development of the thymus from lampreys to chicken and mammals;

• New methods for isolating and culturing of thymus epithelial cells, dendritic, mesenchymal, and endothelial cells, their function and involvement in proper thymus function;

• Studies on small chemical compounds, transcription factors, microRNAs, proteins, and interleukins which influence the thymic function, involution, or regeneration;

• Reversibility of the thymus aging.


Keywords: Thymus, development, T lymphocytes, adult stem cells, epithelial cells, aging, FoxN1, NOTCH


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 September 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 September 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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