PDLIM2 restricts Th1 and Th17 differentiation and prevents autoimmune disease

Zhaoxia Qu,Markus Y Mapara,Jingjiao Zhou,Jing Fu,Michael J Grusby,Huihui Ma,Meihua Jin,Gutian Xiao

doi:10.1186/2045-3701-2-23

Abstract

BackgroundPDLIM2 is essential for the termination of the inflammatory transcription factors NF-κB and STAT but is dispensable for the development of immune cells and immune tissues/organs. Currently, it remains unknown whether and how PDLIM2 is involved in physiologic and pathogenic processes.ResultsHere we report that naive PDLIM2 deficient CD4+ T cells were prone to differentiate into Th1 and Th17 cells. PDLIM2 deficiency, however, had no obvious effect on lineage commitment towards Th2 or Treg cells. Notably, PDLIM2 deficient mice exhibited increased susceptibility to experimental autoimmune encephalitis (EAE), a Th1 and/or Th17 cell-mediated inflammatory disease model of multiple sclerosis (MS). Mechanistic studies further indicate that PDLIM2 was required for restricting expression of Th1 and Th17 cytokines, which was in accordance with the role of PDLIM2 in the termination of NF-κB and STAT activation.ConclusionThese findings suggest that PDLIM2 is a key modulator of T-cell-mediated immune responses that may be targeted for the therapy of human autoimmune diseases.

Highlights

PDZ-LIM domain-containing protein 2 (PDLIM2) is essential for the termination of the inflammatory transcription factors NF-κB and signal transducers and activators of transcription (STAT) but is dispensable for the development of immune cells and immune tissues/organs
PDLIM2 deficiency in CD4+ th cells enhances Th1 and Th17 cell differentiation but has no obvious effect on Th2 and Treg cell differentiation To test whether PDLIM2 is involved in T helper (Th) cell differentiation, naive CD4+ Th cells were isolated from spleens of
These data suggest that PDLIM2 plays a specific role in restricting Th1 and Th17 cell differentiation

Summary

Background

CD4+ T helper (Th) cells play a central role in orchestrating immune responses to diverse microbial pathogens [1]. NF-κB proteins have been well demonstrated [7,8] It still remains largely unknown how activated STAT and NF-κB are terminated for proper Th cell differentiation and immune responses and how STAT and NFκB are deregulated in autoimmune diseases. Previous studies show that PDLIM2, a ubiquitously expressed PDZ-LIM domain-containing protein with high expression in lymphoid tissues and cells including T lymphocytes, is required for the termination of STAT and NF-κB activation [9,10]. Mouse genetic studies reveal that PDLIM2 is not required for the development of immune cells and immune tissues/organs [9]. It remains unknown whether PDLIM2 is involved in the pathogenesis of inflammatory and autoimmune diseases

Results and discussion

Methods

16. Morel L