Th22 cells are expanded in multiple sclerosis and are resistant to IFN-β

J Leukoc Biol. 2014 Dec;96(6):1155-64. doi: 10.1189/jlb.5A0813-463RR. Epub 2014 Aug 5.

Authors

Affiliations

¹ Center for Experimental Research and Medical Studies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, Turin, Italy; Department of Clinical and Biological Sciences.
² Divisions of Neurology and.
³ Department of Medical Sciences, Dermatologic Clinic, University of Turin, Italy.
⁴ Department of Clinical and Experimental Medicine, Second University of Naples, Italy; and.
⁵ Radiology, San Luigi Gonzaga School of Medicine, Orbassano, Italy;
⁶ Human Genetics Foundation, Turin, Italy.
⁷ Center for Experimental Research and Medical Studies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, Turin, Italy; Department of Clinical and Biological Sciences, franco.novelli@unito.it.

PMID: 25097195
DOI: 10.1189/jlb.5A0813-463RR

Abstract

Th1 and Th17 cells have been considered as effectors in mouse EAE and in the human counterpart, MS. Recently, IL-22, a Th17-related, proinflammatory cytokine, has been associated with a new Th cell subset, defined as Th22, involved in chronic inflammatory conditions, such as psoriasis; the role of IL-22 in MS has not yet been elucidated. Here, we report that similar to Th17 cells, the number of Th22 cells increased in the PB and the CSF of RR MS patients, especially during the active phases of the disease. However, as opposed to Th17 cells, the expansion of Th22 cells occurred before the active phases of the disease. Th22 cells were found to be specific for the autoantigen MBP and also expressed high levels of CCR6 and T-bet, as for Th17 cells, indicating that Th22 self-reactive cells could have CNS-homing properties and be pathogenic in active RRMS patients. Conversely to Th17 cells, Th22 cells displayed lower levels of IFNAR1 and were insensitive to IFN-β inhibition. These data suggest that expansion of Th22 cells in MS could be one of the factors that critically influence resistance to IFN-β therapy.

Keywords: CD4 T helper cells; autoimmunity; cytokines; human; interferon receptors; interferons.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autoantigens / immunology
Cell Division
Cells, Cultured
Clone Cells / immunology
Female
Gene Expression Profiling
Humans
Interferon-beta / pharmacology*
Interferon-gamma Release Tests
Interleukin-22
Interleukins / biosynthesis*
Interleukins / genetics
Lymphocyte Activation
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / blood
Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
Multiple Sclerosis, Relapsing-Remitting / immunology*
Myelin Basic Protein / immunology
Primary Cell Culture
Receptors, CCR6 / biosynthesis
Receptors, CCR6 / genetics
Receptors, Chemokine / biosynthesis*
Receptors, Chemokine / genetics
Receptors, Cytokine / biosynthesis*
Receptors, Cytokine / genetics
T-Box Domain Proteins / metabolism
T-Cell Antigen Receptor Specificity
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocyte Subsets / pathology*
Th17 Cells / immunology
Transcription Factors / metabolism*
Young Adult

Substances

Autoantigens
CCR6 protein, human
Interleukins
Myelin Basic Protein
Receptors, CCR6
Receptors, Chemokine
Receptors, Cytokine
T-Box Domain Proteins
T-box transcription factor TBX21
Transcription Factors
Interferon-beta