Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

Patrizia Fasching; Martin Stradner; Winfried Graninger; Christian Dejaco; Johannes Fessler

doi:10.3390/molecules22010134

Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

Molecules. 2017 Jan 14;22(1):134. doi: 10.3390/molecules22010134.

Authors

Patrizia Fasching¹, Martin Stradner², Winfried Graninger³, Christian Dejaco⁴, Johannes Fessler⁵

Affiliations

¹ Department of Rheumatology and Immunology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. patriziafasching@gmx.at.
² Department of Rheumatology and Immunology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. martin.stradner@medunigraz.at.
³ Department of Rheumatology and Immunology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. winfried.graninger@medunigraz.at.
⁴ Department of Rheumatology and Immunology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. christian.dejaco@gmx.net.
⁵ Department of Rheumatology and Immunology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. johannes_fessler@hotmail.com.

Abstract

A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases.

Keywords: Foxp3; RORγt; Th17-cells; autoimmunity; regulatory T-cells.

Publication types

Review

MeSH terms

Animals
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Autoimmune Diseases / drug therapy*
Autoimmune Diseases / genetics
Autoimmune Diseases / immunology
Autoimmune Diseases / pathology
Forkhead Transcription Factors / antagonists & inhibitors
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / immunology*
Gene Expression Regulation
Humans
Immunologic Factors / therapeutic use*
Inflammation
Interleukin-17 / antagonists & inhibitors
Interleukin-17 / genetics
Interleukin-17 / immunology
Nuclear Receptor Subfamily 1, Group F, Member 3 / antagonists & inhibitors
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology*
Piperidines / therapeutic use
Pyrimidines / therapeutic use
Pyrroles / therapeutic use
Signal Transduction
T-Lymphocytes, Regulatory / drug effects*
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / pathology
Th17 Cells / drug effects*
Th17 Cells / immunology
Th17 Cells / pathology
Ustekinumab / therapeutic use

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
FOXP3 protein, human
Forkhead Transcription Factors
Immunologic Factors
Interleukin-17
Nuclear Receptor Subfamily 1, Group F, Member 3
Piperidines
Pyrimidines
Pyrroles
RORC protein, human
sirukumab
tofacitinib
secukinumab
Ustekinumab