TGFβR signalling controls CD103⁺CD11b⁺ dendritic cell development in the intestine

Area of Science:

• Immunology
• Cell Biology
• Gastroenterology

Background:

• Intestinal dendritic cells (DCs) play a critical role in maintaining gut homeostasis.
• The specific developmental pathways for distinct intestinal DC subsets, particularly CD103+CD11b+ DCs, remain incompletely understood.

Purpose of the Study:

• To investigate the role of transforming growth factor receptor 1 (TGFβR1) in the differentiation of intestinal CD103+CD11b+ DCs.
• To identify molecular markers defining the CD103+CD11b+ DC lineage.
• To assess the functional consequences of TGFβR1 signaling deficiency on T cell populations.

Main Methods:

• Utilizing mouse models with targeted deletion of Tgfbr1 in specific cell populations (CD11c-Cre.Tgfbr1fl/fl mice).
• Employing flow cytometry to analyze DC subsets (CD103+CD11b+ and CD103-CD11b+).
• Performing transcriptional profiling to identify lineage-specific markers.
• Assessing T cell populations (regulatory T cells and Th17 cells) in vitro and in vivo.

Main Results:

• Deletion of Tgfbr1 significantly reduces the number of intestinal CD103+CD11b+ DCs.
• A reciprocal increase in the CD103-CD11b+ DC subset was observed.
• Transcriptional profiling identified CD101, TREM1, and Siglec-F as markers for the CD103+CD11b+ DC lineage.
• The absence of CD103+CD11b+ DCs resulted from defective differentiation from CD103-CD11b+ precursors.
• Reduced generation of antigen-specific regulatory T cells and lower numbers of endogenous Th17 cells were observed.

Conclusions:

• TGFβR1 signaling is essential for the cell-intrinsic development of intestinal CD103+CD11b+ DCs.
• TGFβR1 signaling mediates the differentiation of CD103-CD11b+ DCs into the CD103+CD11b+ subset.
• These unique DCs play a role in the generation of regulatory T cells and Th17 cells, highlighting TGFβR1's importance in immune regulation within the intestine.