Mesenteric lymph node CD11b - CD103 + PD-L1 High dendritic cells highly induce regulatory T cells

• Published in: Immunology 2017-09, Vol.152 (1), p.52-64
• Main Authors: Shiokawa, Aya, Kotaki, Ryutaro, Takano, Tomohiro, Nakajima-Adachi, Haruyo, Hachimura, Satoshi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aldehyde Dehydrogenase - immunology; Aldehyde Dehydrogenase - metabolism; Animals; Antigens, CD - immunology; Antigens, CD - metabolism; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; CD11b Antigen - immunology; CD11b Antigen - metabolism; Cell Communication - drug effects; Cell Movement; Cells, Cultured; Coculture Techniques; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Immunity, Mucosal; Integrin alpha Chains - immunology; Integrin alpha Chains - metabolism; Integrin beta Chains - immunology; Integrin beta Chains - metabolism; Intestines - cytology; Intestines - drug effects; Intestines - immunology; Intestines - metabolism; Lymph Nodes - cytology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymph Nodes - metabolism; Mesentery; Mice, Inbred BALB C; Ovalbumin - administration & dosage; Ovalbumin - immunology; Phenotype; Signal Transduction; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; Tretinoin - pharmacology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12747

Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3 regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that the CD103 DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from programmed death ligand 1 (PD-L1) -deficient mice could not induce regulatory T cells. Hence, the present study investigated the expression of these molecules on MLN CD11c cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b CD103 PD-L1 , CD11b CD103 PD-L1 , CD11b CD103 PD-L1 and CD11b CD103 PD-L1 . Among them, the CD11b CD103 PD-L1 DC subset highly induced Foxp3 T cells. This subset expressed Aldh1a2 and Itgb8 genes, which are involved in retinoic acid metabolism and transforming growth factor-β (TGF-β) activation, respectively. Exogenous TGF-β supplementation equalized the level of Foxp3 T-cell induction by the four subsets whereas retinoic acid did not, which suggests that high ability to activate TGF-β is determinant for the high Foxp3 T-cell induction by CD11b CD103 PD-L1 DC subset. Finally, this subset exhibited a migratory DC phenotype and could take up and present orally administered antigens. Collectively, the MLN CD11b CD103 PD-L1 DC subset probably takes up luminal antigens in the intestine, migrates to MLNs, and highly induces regulatory T cells through TGF-β activation.