Increased CD1c+ mDC1 with mature phenotype regulated by TNFα-p38 MAPK in autoimmune ocular inflammatory disease

Ping Chen, Alastair Denniston, Susan Hannes, William Tucker, Lai Wei, Baoying Liu, Tiaojiang Xiao, Sima Hirani, Zhiyu Li, Shayma Jawad, Han Si, Richard W J Lee, H Nida Sen, Robert B Nussenblatt

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)

Abstract

In this study we investigated the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c(+) mDC1 in uveitis patients. The increased CD1c(+) mDC1 exhibited high HLADR expression and less antigen uptake. CD1c(+) mDC1 were divided into two subpopulations. CD1c(hi) mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1c(lo) mDC1 subpopulation. Importantly, the CD1c(hi) mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD4(+)CD62L(-) T helper cell proliferation. The mature phenotype and function of CD1c(+) mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c(+) mDC1.

Original languageEnglish
Pages (from-to)35-46
Number of pages12
JournalClinical Immunology
Volume158
Issue number1
DOIs
Publication statusPublished - May 2015

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD1
  • Autoimmune Diseases
  • Dendritic Cells
  • Female
  • Glycoproteins
  • Humans
  • Male
  • Middle Aged
  • Myeloid Cells
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer
  • Tumor Necrosis Factor-alpha
  • Uveitis
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases

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