OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response Academic Article uri icon

Overview

MeSH Major

  • Lupus Erythematosus, Systemic
  • Myeloid Cells
  • OX40 Ligand
  • Receptors, OX40
  • T-Lymphocytes, Helper-Inducer

abstract

  • Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.

authors

publication date

  • June 16, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4570857

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2015.05.012

PubMed ID

  • 26070486

Additional Document Info

start page

  • 1159

end page

  • 70

volume

  • 42

number

  • 6