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Published on: August 13, 2013
Alterations of Thymus-Derived Tregs in Multiple Sclerosis
Tiziana Lorenzini1, Wolfgang Faigle1, Josefine Ruder1
1From the Neuroimmunology and MS Research (T.L., W.F., J.R., M.J.D., R.M.), Neurology Clinic, University Hospital Zurich; Division of Immunology (T.L.), University Children's Hospital Zurich, University of Zurich; Cellerys AG (W.F., R.M.), Schlieren, Switzerland; Immunity and Cancer (U932) (W.F.), Immune Response to Cancer Laboratory, Institut Curie, 26 rue d'Ulm, CEDEX 05, Paris, France; Functional Genomics Center Zurich (L.O.), Swiss Federal Institute of Technology and University of Zurich; Institute of Experimental Immunology (R.M.), University of Zurich, Switzerland; and Therapeutic Design Unit (R.M.), Center for Molecular Medicine, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Regulatory T cells (Tregs) show dysfunction in multiple sclerosis (MS), with altered function and transcriptomes observed, particularly in thymus-derived Tregs, impacting disease understanding.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Cellular Immunology
Background:
- Multiple sclerosis (MS) is a primary autoimmune central nervous system (CNS) disease.
- It is a leading cause of chronic neurological disability in young adults.
- Both B cells and T cells are implicated in MS pathogenesis, but regulatory T cell (Treg) involvement requires further clarification.
Purpose of the Study:
- To investigate alterations in regulatory T cells (Tregs) within the context of multiple sclerosis (MS).
- To elucidate the specific roles and functional changes of Treg subsets in MS patients.
Main Methods:
- Analysis of Treg compartments in 41 relapsing-remitting MS patients and 17 healthy controls.
- Utilized multiple experimental approaches to examine Treg alterations.
Main Results:
- MS patients exhibited reduced frequencies of CD4+ T cells and Foxp3+ Tregs, with age-dependent Treg subset variations.
- Treg suppressive function was impaired in natalizumab-treated MS patients, but not in untreated or anti-CD20-treated patients.
- Natalizumab treatment correlated with increased proinflammatory cytokines and altered transcriptomes in thymus-derived Tregs (t-Tregs).
Conclusions:
- Treg dysfunction in MS may stem from an altered t-Treg transcriptome and a proinflammatory milieu.
- These findings enhance the understanding of Treg subtypes and their contribution to MS pathogenesis.
