CCR9 signaling in dendritic cells drives the differentiation of Foxp3 + Tregs and suppresses the allergic IgE response in the gut
Autor: | Manisha Pathak, Namrita Halder, Sandip Ashok Sonar, Priyanka Padghan, Shilpi, Girdhari Lal, Neeraja Kulkarni |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
CD86 Adoptive cell transfer Thymic stromal lymphopoietin biology Immunology FOXP3 hemic and immune systems chemical and pharmacologic phenomena Immunoglobulin E Cell biology 03 medical and health sciences Chemokine receptor 030104 developmental biology 0302 clinical medicine Immune system biology.protein Immunology and Allergy CCL25 030215 immunology |
Zdroj: | European Journal of Immunology. 50:404-417 |
ISSN: | 1521-4141 0014-2980 |
Popis: | 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. |
Databáze: | OpenAIRE |
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