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Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Dec 23; Vol. 11, pp. 607175. Date of Electronic Publication: 2020 Dec 23 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Achieving immunoregulation via in vivo expansion of Foxp3 <superscript>+</superscript> regulatory CD4 <superscript>+</superscript> T cells (Treg) remains challenging. We have shown that mobilization confers to multipotent hematopoietic progenitors (MPPs) the capacity to enhance Treg proliferation. Transcriptomic analysis of Tregs co-cultured with MPPs revealed enhanced expression of genes stabilizing the suppressive function of Tregs as well as the activation of IL-1β-driven pathways. Adoptive transfer of only 25,000 MPPs effectively reduced the development of experimental autoimmune encephalomyelitis (EAE), a pre-clinical model for multiple sclerosis (MS). Production of the pathogenic cytokines IL-17 and GM-CSF by spinal cord-derived CD4 <superscript>+</superscript> T-cells in MPP-protected recipients was reduced while Treg expansion was enhanced. Treg depletion once protection by MPPs was established, triggered disease relapse to the same level as in EAE mice without MPP injection. The key role of IL-1β was further confirmed in vivo by the lack of protection against EAE in recipients of IL-1β-deficient MPPs. Mobilized MPPs may thus be worth considering for cell therapy of MS either per se or for enrichment of HSC grafts in autologous bone marrow transplantation already implemented in patients with severe refractory multiple sclerosis.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2020 Korniotis, D’Aveni, Hergalant, Letscher, Tejerina, Gastineau, Agbogan, Gras, Fouquet, Rossignol, Chèvre, Cagnard, Rubio, Hermine and Zavala.)
- Subjects :
- Animals
Autoimmunity
Cells, Cultured
Coculture Techniques
Cytokines genetics
Cytokines metabolism
Encephalomyelitis, Autoimmune, Experimental genetics
Encephalomyelitis, Autoimmune, Experimental immunology
Encephalomyelitis, Autoimmune, Experimental metabolism
Female
Forkhead Transcription Factors genetics
Forkhead Transcription Factors metabolism
Interleukin-1beta genetics
Interleukin-1beta metabolism
Mice, Inbred C57BL
Mice, Knockout
Multipotent Stem Cells metabolism
Spinal Cord metabolism
T-Lymphocytes, Regulatory metabolism
Transcriptome
Adoptive Transfer
Cell Proliferation
Encephalomyelitis, Autoimmune, Experimental prevention & control
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Lymphocyte Activation
Multipotent Stem Cells immunology
Spinal Cord immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33424854
- Full Text :
- https://doi.org/10.3389/fimmu.2020.607175