Thymic Microenvironment: Interactions Between Innate Immune Cells and Developing Thymocytes

Abstract

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.

CD11c regulates late-stage T cell development in the thymus

“…Successful TCR β chain rearrangement delivers proliferation signals and instructs the transition of DN cells into DP cells. This event is followed by positive selection by thymic epithelial cells (TECs) in the cortex and negative selection by DCs in the medullary region, responding to strong TCR-MHC interactions ( 28 ). Those DP cells with non-functional TCR-MHC interactions undergo death by neglect, which occurs for over 95% of DPs ( 29 ).…”

“…Regarding the role of DCs in thymic T cell development, controversial reports have been made. On one side, thymic DCs have been deemed as a major player that mediates negative selection to induce the apoptosis of DP cells ( 28 , 30 , 31 ); on the other side, thymic DCs were also reported to be involved in positive selection, thus to maintain the survival of DP cells ( 32 , 33 ). The discovery that CD11c plays an essential role in maintaining the survival of T cells suggests that, in addition to MHC-II molecule, DCs could use CD11c to maintain T cell survival.…”

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

“…These intricate selection processes rely on the precise organization and compartmentalization of parenchymal cells facilitating interactions and signaling pathways inside the thymus ( 39 ). The thymic microenvironment includes nerves/nerve fibers, which are believed to regulate T cell development and thymic endocrine function by influencing the secretion of self-hormones such as thymulin, thymopoietin, and thymosins ( 40 , 41 ).…”

Epigallocatechin gallate (EGCG) alleviates the inflammatory response and recovers oral microbiota in acetic acid-induced oral inflammation mice

“…The thymus plays a crucial role in the differentiation and development of T-cells and is the residence of many cell types. 46 A variety of immune cells reside in the spleen, such as neutrophils, macrophages, natural killer (NK) cells, monocytes, dendritic cells (DCs) and gamma delta (γδ) T cells. 47 A study reported that the overexpression of TNF-α led to spleen inflammation in the laying hen, causing spleen damage.…”