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Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis
BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protect...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362604/ https://www.ncbi.nlm.nih.gov/pubmed/34385365 http://dx.doi.org/10.1212/NXI.0000000000001065 |
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author | Carrión, Belinda Liu, Yawei Hadi, Mahdieh Lundstrom, Jon Christensen, Jeppe Romme Ammitzbøll, Cecilie Dziegiel, Morten Hanefeld Sørensen, Per Soelberg Comabella, Manuel Montalban, Xavier Sellebjerg, Finn Issazadeh-Navikas, Shohreh |
author_facet | Carrión, Belinda Liu, Yawei Hadi, Mahdieh Lundstrom, Jon Christensen, Jeppe Romme Ammitzbøll, Cecilie Dziegiel, Morten Hanefeld Sørensen, Per Soelberg Comabella, Manuel Montalban, Xavier Sellebjerg, Finn Issazadeh-Navikas, Shohreh |
author_sort | Carrión, Belinda |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protective invariant natural killer T cell (iNKT cell) subset. METHODS: We performed a transcriptomic and functional analysis of iNKT cells that were reactive to a human collagen type II self-peptide, hCII707-721, measuring differentially induced genes, cytokines, and suppressive capacity. RESULTS: We report the first transcriptomic profile of human conventional vs novel hCII707-721–reactive iNKT cells. We determined that hCII707-721 induces protective iNKT cells that are found in the blood of healthy individuals but not progressive patients with MS (PMS). By transcriptomic analysis, we observed that hCII707-721 promotes their development and proliferation, favoring the splicing of full-length AKT serine/threonine kinase 1 (AKT1) and effector function of this unique lineage by upregulating tumor necrosis factor (TNF)-related genes. Furthermore, hCII707-721–reactive iNKT cells did not upregulate interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-13, or IL-17 by RNA-seq or at the protein level, unlike the response to the glycolipid alpha-galactosylceramide. hCII707-721–reactive iNKT cells increased TNFα only at the protein level and suppressed autologous-activated T cells through FAS-FAS ligand (FAS-FASL) and TNFα-TNF receptor I signaling but not TNF receptor II. DISCUSSION: Based on their immunomodulatory properties, NKT cells have a potential value in the treatment of autoimmune diseases, such as MS. These significant findings suggest that endogenous peptide ligands can be used to expand iNKT cells, without causing a cytokine storm, constituting a potential immunotherapy for autoimmune conditions, including PMS. |
format | Online Article Text |
id | pubmed-8362604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-83626042021-08-13 Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis Carrión, Belinda Liu, Yawei Hadi, Mahdieh Lundstrom, Jon Christensen, Jeppe Romme Ammitzbøll, Cecilie Dziegiel, Morten Hanefeld Sørensen, Per Soelberg Comabella, Manuel Montalban, Xavier Sellebjerg, Finn Issazadeh-Navikas, Shohreh Neurol Neuroimmunol Neuroinflamm Article BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protective invariant natural killer T cell (iNKT cell) subset. METHODS: We performed a transcriptomic and functional analysis of iNKT cells that were reactive to a human collagen type II self-peptide, hCII707-721, measuring differentially induced genes, cytokines, and suppressive capacity. RESULTS: We report the first transcriptomic profile of human conventional vs novel hCII707-721–reactive iNKT cells. We determined that hCII707-721 induces protective iNKT cells that are found in the blood of healthy individuals but not progressive patients with MS (PMS). By transcriptomic analysis, we observed that hCII707-721 promotes their development and proliferation, favoring the splicing of full-length AKT serine/threonine kinase 1 (AKT1) and effector function of this unique lineage by upregulating tumor necrosis factor (TNF)-related genes. Furthermore, hCII707-721–reactive iNKT cells did not upregulate interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-13, or IL-17 by RNA-seq or at the protein level, unlike the response to the glycolipid alpha-galactosylceramide. hCII707-721–reactive iNKT cells increased TNFα only at the protein level and suppressed autologous-activated T cells through FAS-FAS ligand (FAS-FASL) and TNFα-TNF receptor I signaling but not TNF receptor II. DISCUSSION: Based on their immunomodulatory properties, NKT cells have a potential value in the treatment of autoimmune diseases, such as MS. These significant findings suggest that endogenous peptide ligands can be used to expand iNKT cells, without causing a cytokine storm, constituting a potential immunotherapy for autoimmune conditions, including PMS. Lippincott Williams & Wilkins 2021-08-12 /pmc/articles/PMC8362604/ /pubmed/34385365 http://dx.doi.org/10.1212/NXI.0000000000001065 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Carrión, Belinda Liu, Yawei Hadi, Mahdieh Lundstrom, Jon Christensen, Jeppe Romme Ammitzbøll, Cecilie Dziegiel, Morten Hanefeld Sørensen, Per Soelberg Comabella, Manuel Montalban, Xavier Sellebjerg, Finn Issazadeh-Navikas, Shohreh Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title_full | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title_fullStr | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title_full_unstemmed | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title_short | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
title_sort | transcriptome and function of novel immunosuppressive autoreactive invariant natural killer t cells that are absent in progressive multiple sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362604/ https://www.ncbi.nlm.nih.gov/pubmed/34385365 http://dx.doi.org/10.1212/NXI.0000000000001065 |
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