Type 2 cytokines in the thymus activate Sirpα + dendritic cells to promote clonal deletion.
Elise R BreedMatouš VobořilKatherine M AshbyRyan J MartinezLily QianHaiguang WangOscar C SalgadoChristine H O'ConnorKristin A HogquistPublished in: Nature immunology (2022)
The thymus contains a diversity of dendritic cells (DCs) that exist in defined locations and have different antigen-processing and -presenting features. This suggests that they play nonredundant roles in mediating thymocyte selection. In an effort to eliminate SIRPα + classic DC2 subsets, we discovered that a substantial proportion expresses the surface lectin, CD301b, in the thymus. These cells resemble the CD301b + type 2 immune response promoting DCs that are present in the skin-draining lymph nodes. Transcriptional and phenotypic comparison to other DC subsets in the thymus revealed that thymic CD301b + cDCs represent an activated state that exhibits enhanced antigen processing and presentation. Furthermore, a CD301b + cDC2 subset demonstrated a type 2 cytokine signature and required steady-state interleukin-4 receptor signaling. Selective ablation of CD301b + cDC2 subsets impaired clonal deletion without affecting regulatory T cells (T reg cells). The T cell receptor α repertoire sequencing confirmed that a cDC2 subset promotes deletion of conventional T cells with minimal effect on T reg cell selection. Together, these findings suggest that cytokine-induced activation of DCs in the thymus substantially enforces central tolerance.
Keyphrases
- dendritic cells
- regulatory t cells
- immune response
- induced apoptosis
- single cell
- lymph node
- nk cells
- peripheral blood
- case report
- cell cycle arrest
- cell proliferation
- gene expression
- cell cycle
- bone marrow
- inflammatory response
- mesenchymal stem cells
- early stage
- high glucose
- soft tissue
- endothelial cells
- heat shock
- wound healing
- diabetic rats
- stress induced