The thymic microenvironment gradually modulates the phenotype of thymus‐homing peripheral conventional dendritic cells

• Published in: Immunity, Inflammation and Disease Vol. 10; no. 2; pp. 175 - 188
• Main Authors: Herppich, Susanne, Beckstette, Michael, Huehn, Jochen
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2022; John Wiley and Sons Inc; Wiley
• Subjects: Animal sciences; Animal welfare; Antibodies; Antigens; Dendritic cells; Genotype & phenotype; Laboratory animals; Lymphocytes; Original; Pore size; RTOC; splenic cDCs; T cell receptors; thymic cDCs; thymus; Thymus gland; Treg cell; Zoology; RTOC; splenic cDCs; thymic cDCs; thymus; Treg cell
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.559

Background & Aims Thymic conventional dendritic cells (t‑DCs) are crucial for the development of T cells. A substantial fraction of t‑DCs originates extrathymically and migrates to the thymus. Here, these cells contribute to key processes of central tolerance like the clonal deletion of self‑reactive thymocytes and the generation of regulatory T (Treg) cells. So far, it is only incompletely understood which impact the thymic microenvironment has on thymus‑homing conventional DCs (cDCs), which phenotypic changes occur after the entry of peripheral cDCs into the thymus and which functional properties these modulated cells acquire. Materials & Methods In the present study, we mimicked the thymus‑homing of peripheral cDCs by introducing ex vivo isolated splenic cDCs (sp‑DCs) into reaggregated thymic organ cultures (RTOCs). Results Already after two days of culture, the transcriptomic profile of sp‑DCs was modulated and had acquired certain key signatures of t‑DCs. The regulated genes included immunomodulatory cytokines and chemokines as well as costimulatory molecules. After four days of culture, sp‑DCs appeared to have at least partially acquired the peculiar Treg cell‐inducing capacity characteristic of t‑DCs. Discussion & Conclusion Taken together, our findings indicate that peripheral cDCs possess a high degree of plasticity enabling them to quickly adapt to the thymus‐specific microenvironment. We further provide indirect evidence that thymus‐specific properties such as the efficient induction of Treg cells under homeostatic conditions can be partially transferred to thymus‑homing peripheral cDC subsets. Thymic conventional dendritic cells (t‐DCs) are crucial for the development of T cells and central tolerance. A substantial fraction of t‐DCs originates extrathymically and migrates to the thymus. Here, we used reaggregated thymic organ cultures (RTOCs) to demonstrate that these thymus‐homing DCs are plastic and can acquire essential thymus‐specific properties upon entry into the thymus.