Type I IFN signaling in T regulatory cells modulates chemokine production and myeloid derived suppressor cells trafficking during EAE
| Autor: | Eric Dahlstrom, Lydia Sykora, Ethan M. Shevach, Amina Metidji, Kishore Kanakabandi, Cihan Oguz, Kent D. Barbian, Shalini Tanwar |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chemokine endocrine system Encephalomyelitis Autoimmune Experimental Multiple Sclerosis medicine.medical_treatment Immunology Receptor Interferon alpha-beta CCL8 T-Lymphocytes Regulatory Article 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Chemokine CCL8 Humans 030203 arthritis & rheumatology Chemokine CCL22 Mice Knockout biology Myeloid-Derived Suppressor Cells Experimental autoimmune encephalomyelitis FOXP3 Macrophage Inflammatory Proteins medicine.disease 030104 developmental biology CCL9 Cytokine Chemokines CC Interferon Type I Cancer research biology.protein Myeloid-derived Suppressor Cell Lymph Nodes CCL22 Signal Transduction |
| Zdroj: | J Autoimmun |
| ISSN: | 1095-9157 |
| Popis: | Interferon-β has therapeutic efficacy in Multiple Sclerosis by reducing disease exacerbations and delaying relapses. Previous studies have suggested that the effects of type I IFN in Experimental Autoimmune Encephalomyelitis (EAE) in mice were targeted to myeloid cells. We used mice with a conditional deletion(cKO) of the type I IFN receptor (IFNAR) in T regulatory (Treg) cells to dissect the role of IFN signaling on Tregs. cKO mice developed severe EAE with an earlier onset than control mice. Although Treg cells from cKO mice were more activated, the activation status and effector cytokine production of CD4(+)Foxp3(−) T cells in the draining lymph nodes (dLN) was similar in WT and cKO mice during the priming phase. Production of chemokines (CCL8, CCL9, CCL22) by CD4(+)Foxp3(−) T cells and LN resident cells from cKO mice was suppressed. Suppression of chemokine production was accompanied by a substantial reduction of myeloid derived suppressor cells (MDSCs) in the dLN of cKO mice, while generation of MDSCs and recruitment to peripheral organs was comparable. This study demonstrates that signaling by type I IFNs in Tregs reduces their capacity to suppress chemokine production, with resultant alteration of the entire microenvironment of draining lymph nodes leading to enhancement of MDSC homing, and beneficial effects on disease outcome. |
| Databáze: | OpenAIRE |
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