Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis

Pavanish Kumar, Leong Jing Yao, Suzan Saidin, Bhairav Paleja, Jorg van Loosdregt, Camillus Chua, Thaschawee Arkachaisri, Alessandro Consolaro, Marco Gattorno, Alberto Martini, Ken D. Pischel, Gary W. Williams, Martin Lotz, Salvatore Albani

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis. We demonstrated “Autophagic memory” as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased autophagy. The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalJournal of Autoimmunity
Volume94
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Autophagy
Arthritis
T-Lymphocytes
RNA Sequence Analysis
Gene Regulatory Networks
T-Lymphocyte Subsets
Starvation
Methylation
Rheumatoid Arthritis
Transcription Factors
Cell Line
Survival

Keywords

  • Autophagic memory
  • Inflammation
  • MYC
  • Pathogenic T cells
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kumar, P., Yao, L. J., Saidin, S., Paleja, B., van Loosdregt, J., Chua, C., ... Albani, S. (2018). Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis. Journal of Autoimmunity, 94, 90-98. https://doi.org/10.1016/j.jaut.2018.07.014

Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis. / Kumar, Pavanish; Yao, Leong Jing; Saidin, Suzan; Paleja, Bhairav; van Loosdregt, Jorg; Chua, Camillus; Arkachaisri, Thaschawee; Consolaro, Alessandro; Gattorno, Marco; Martini, Alberto; Pischel, Ken D.; Williams, Gary W.; Lotz, Martin; Albani, Salvatore.

In: Journal of Autoimmunity, Vol. 94, 01.11.2018, p. 90-98.

Research output: Contribution to journalArticle

Kumar, P, Yao, LJ, Saidin, S, Paleja, B, van Loosdregt, J, Chua, C, Arkachaisri, T, Consolaro, A, Gattorno, M, Martini, A, Pischel, KD, Williams, GW, Lotz, M & Albani, S 2018, 'Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis', Journal of Autoimmunity, vol. 94, pp. 90-98. https://doi.org/10.1016/j.jaut.2018.07.014
Kumar, Pavanish ; Yao, Leong Jing ; Saidin, Suzan ; Paleja, Bhairav ; van Loosdregt, Jorg ; Chua, Camillus ; Arkachaisri, Thaschawee ; Consolaro, Alessandro ; Gattorno, Marco ; Martini, Alberto ; Pischel, Ken D. ; Williams, Gary W. ; Lotz, Martin ; Albani, Salvatore. / Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis. In: Journal of Autoimmunity. 2018 ; Vol. 94. pp. 90-98.
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