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Thursday, February 15th, 2018
Table of Contents

1 Introduction
5 PMID
 [F] Diseases Research  / PubMed Research Articles  /
Augmented Th17 Differentiation Leads to Cutaneous and Synovio-Entheseal Inflammation in a Novel Model of Psoriatic Arthritis.

PubMed

 

Resource

Arthritis & rheumatology (Hoboken, N.J.) Feb ; ()

Authors

Yang L1; Fanok MH2; Mediero-Munoz A3; Fogli LK4; Corciulo C5; Abdollahi S6; Cronstein BN7; Scher JU8; Koralov SB9;

Author Information
  • 1Department of Pathology, NYU School of Medicine, New York, NY, 10016.
  • 2Department of Pathology, NYU School of Medicine, New York, NY, 10016.
  • 3Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10016.
  • 4Department of Pathology, NYU School of Medicine, New York, NY, 10016.
  • 5Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10016.
  • 6Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10016.
  • 7Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10016.
  • 8Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10016.
  • 9Department of Pathology, NYU School of Medicine, New York, NY, 10016.

Abstract

OBJECTIVE: To introduce a novel pre-clinical animal model of psoriatic arthritis, R26STAT3Cstopfl/flCD4Cre mice, and investigate the role of Th17 cytokines in the disease pathogenesis.

METHODS: We characterized a novel murine model of Th17-driven cutaneous and synovio-entheseal disease directed by T cell-specific expression of a hyperactive STAT3 allele. By crossing R26STAT3Cstopfl/flCD4Cre mice onto an IL-22 knockout background or treating them with a neutralizing antibody against IL-17, we interrogated how these Th17 cytokines contribute to disease pathogenesis.

RESULTS: R26STAT3Cstopfl/flCD4Cre mice develop acanthosis, hyperkeratosis, and parakeratosis of the skin, as well as, enthesitis/tendonitis and peri-articular bone erosion in different joints accompanied by osteopenia. T cell-specific expression of a hyperactive STAT3C allele drives an augmented Th17 response in these animals. Careful characterization revealed an increase in osteoclast progenitor (OCP) cells and RANKL producing cells that contributed to the osteopenic phenotype observed in the mutant animals. Abrogation of Th17 cytokines, IL-17 or IL-22, improved both skin and bone phenotype in the R26STAT3Cstopfl/flCD4Cre mice, revealing a central role of Th17 cells in the regulation of OCP numbers and RANKL expression on stromal cells.

CONCLUSION: Perturbation of the IL-23/Th17 axis instigates Th17-mediated inflammation in R26STAT3Cstopfl/flCD4Cre mice, leading to cutaneous and synovio-entheseal inflammation, and bone pathology highly reminiscent of psoriatic arthritis. Both IL-17A and IL-22 produced by Th17 cells play critical roles in promoting the cutaneous and musculoskeletal inflammation that characterizes psoriatic arthritis.. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID

29439292

Others

Publication Type: Journal Article


This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.


Last Modified:   2016-03-27


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