| First Author | Pathak M | Year | 2020 |
| Journal | Eur J Immunol | Volume | 50 |
| Issue | 3 | Pages | 404-417 |
| PubMed ID | 31755547 | Mgi Jnum | J:288853 |
| Mgi Id | MGI:6416357 | Doi | 10.1002/eji.201948327 |
| Citation | Pathak M, et al. (2020) CCR9 signaling in dendritic cells drives the differentiation of Foxp3(+) Tregs and suppresses the allergic IgE response in the gut. Eur J Immunol 50(3):404-417 |
| abstractText | The chemokine receptor CCR9 and its only known ligand CCL25 play an important role in gut inflammation and autoimmune colitis. The function of CCR9-CCL25 in the migration of immune cells is well characterized. However, its role in the immune cell differentiation is mostly not known. Using dextran sodium sulfate (DSS)-induced gut inflammation model, we showed that CCR9(+) dendritic cells (DCs) specifically CD11b(-) CD103(+) DCs were significantly increased in the gut-associated lymphoid tissues (GALT) compared to control mice. These CCR9(+) DCs express lower MHC II and CD86 molecules and had regulatory surface markers (FasL and latency-associated peptide, LAP) in the GALT. In the presence of CCL25, CCR9(+) DCs promoted in vitro differentiation of Foxp3(+) regulatory CD4(+) T cells (Tregs). CCL25-induced differentiation of Tregs was due to intrinsic signaling in the DCs but not through CD4(+) T cells, which was driven by the production of thymic stromal lymphopoietin (TSLP) and not IL-10. Furthermore, adoptive transfer of CCR9(+) DCs in C57BL/6 mice promoted Tregs but reduced the Th17 cells in the GALT, and also suppressed the OVA-specific gut-allergic response. Our results suggest CCR9(+) DCs have a regulatory function and may provide a new cellular therapeutic strategy to control gut inflammation and allergic immune reaction. |
