About this Research Topic
The thymus remains a complex lymphoid organ based on its unique role in supporting the development of T cells recognizing but not overtly responding to self-peptide-self MHC molecules. This process relies on two major thymic epithelial cell (TECs) subsets, termed cortical and medullary TECs. The commanding role of TECs is supported by additional interactions with mesenchymal- and endothelial- derived cell subsets along with hematopoietic cells. With a maximal output of T cells by adolescence, the thymus undergoes a subsequent age-dependent atrophy coupled with cell transitions and adipogenesis. Malnutrition, stress, infections, and immunodeficiencies all cause a transient and sometimes permanent thymic hypoplasia. The regenerative capacity of this tissue is remarkable but can be masked by pathophysiological changes leading to hyperplasia. Thus, autoimmune diseases and oncogenic transformations can lead to thymomas and thymic carcinomas. Surgical resection of the enlarged thymuses is the cornerstone treatment for operable thymic epithelial tumors and certain autoimmune conditions. Thymus removal is also sometimes performed during cardiac surgeries with the increasing mortality and cancer risks. Thus novel and precision treatments and regenerative therapies are urgently needed to restore T cell development. Understanding the contributions of the many cell subsets that coordinate thymic growth, regeneration, thymopoiesis and tumorigenesis are essential for precision medicine strategies to correct thymic dysfunctions.
Deciphering the molecular mechanisms controlling thymus development, thymopoiesis and tissue regeneration is needed to improve T cell output for various clinical conditions, including aging. Moreover, understanding the genetic changes and the origin of transformed cells in the tissue leading to hyperplasia and tumor progression are essential for both early diagnosis and development of novel and precision therapies. In this research collection, our aim is to address these issues, covering topics from thymic formation and function, stromal and hematopoietic cell subsets, aging related tissue involution and tumor initiation/progression of varying histological types. We will report new discoveries in the field and collect experts’ opinions on achievement in the past decades and on future directions for research of normal and diseased thymus.
In this Research Topic, we welcome all article types with a focus on:
· Regulation of thymopoiesis including the contributions of TECs, mesenchymal cells, endothelial cells, and hematopoietic cells such as dendritic cells and innate lymphoid cells
· In-born Errors of Immunity leading to thymic hypoplasia/aplasia such as PAX1, FOXN1, TBX1, TP63, 22q11.2, gestational diabetes, gestational retinopathy, CHARGE
· Progress in Organoid Development: In vitro and in vivo approaches to improve T cell development
· Thymus output diagnostics: TRECs and T cell output, aging, infections,
· Therapeutics: Implant vs Transplant, BMT, Treg production, cytokine therapies
· Autoimmunity: myasthenia gravis, ulcerative colitis, Bechet’s disease and consequent impacts on thymus functions
· Tumorigenesis: key genetic alterations, cells of origin of thymic epithelial tumors, histological subtypes and preclinical models (Cell lines, organoids and animal models).
· Clinical perspectives: radiological exposures, chemotherapy, immunotherapy, postnatal thymectomy consequences on immunity.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Deciphering the molecular mechanisms controlling thymus development, thymopoiesis and tissue regeneration is needed to improve T cell output for various clinical conditions, including aging. Moreover, understanding the genetic changes and the origin of transformed cells in the tissue leading to hyperplasia and tumor progression are essential for both early diagnosis and development of novel and precision therapies. In this research collection, our aim is to address these issues, covering topics from thymic formation and function, stromal and hematopoietic cell subsets, aging related tissue involution and tumor initiation/progression of varying histological types. We will report new discoveries in the field and collect experts’ opinions on achievement in the past decades and on future directions for research of normal and diseased thymus.
In this Research Topic, we welcome all article types with a focus on:
· Regulation of thymopoiesis including the contributions of TECs, mesenchymal cells, endothelial cells, and hematopoietic cells such as dendritic cells and innate lymphoid cells
· In-born Errors of Immunity leading to thymic hypoplasia/aplasia such as PAX1, FOXN1, TBX1, TP63, 22q11.2, gestational diabetes, gestational retinopathy, CHARGE
· Progress in Organoid Development: In vitro and in vivo approaches to improve T cell development
· Thymus output diagnostics: TRECs and T cell output, aging, infections,
· Therapeutics: Implant vs Transplant, BMT, Treg production, cytokine therapies
· Autoimmunity: myasthenia gravis, ulcerative colitis, Bechet’s disease and consequent impacts on thymus functions
· Tumorigenesis: key genetic alterations, cells of origin of thymic epithelial tumors, histological subtypes and preclinical models (Cell lines, organoids and animal models).
· Clinical perspectives: radiological exposures, chemotherapy, immunotherapy, postnatal thymectomy consequences on immunity.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Keywords: Development, Tumorigenesis, Cell of origin, Gene alterations, Thymic epithelial cells, Thymic epithelial tumors, Precision therapies, Thymus Development, Mesenchymal cells, Endothelial cells, In-born errors of immunity, Thymus Transplants, Autoimmunity, Thymic organoids, Myasthenia Gravis
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.
