A critical role for expression of atypical chemokine receptor 2 in multiple sclerosis: A preliminary project

Mult Scler Relat Disord. 2020 Feb:38:101524. doi: 10.1016/j.msard.2019.101524. Epub 2019 Nov 14.

Abstract

Background: ACKR2 is an atypical chemokine receptor that promotes acute inflammation by acting as a scavenger receptor for inflammatory chemokines in experimental models of some inflammatory disorders, but its function in multiple sclerosis (MS) is unclear. Therefore we aimed to evaluate the mRNA expression of ACKR2 as a scavenger receptor in patients with MS and also the correlation of this expression with certain cytokines that are important for MS pathogenesis.

Methods: The ACKR2 mRNA expression was examined on peripheral blood mononuclear cells (PBMCs) of 40 patients with relapsing-remitting MS (RRMS) and 35 healthy individuals. ACKR2 mRNA expressions were measured using real-time quantitative polymerase chain reaction (qPCR). In addition, circulating cytokine levels (TNF-α, IL-6, IL-33) in all patients and controls were evaluated using enzyme-linked immunosorbent assay.

Results: mRNA expression of ACKR2 was decreased on PBMCs compared to healthy subjects (p < 0.001). ACKR2 expression in peripheral blood leucocytes could be regulated by circulating cytokines but there are no correlations with these cytokines (p > 0.05). In addition, the patients' plasma levels of IL-33 significantly increased (p = 0.039) and no significant difference was found between other cytokine levels in the patients (p > 0.05).

Conclusion: Our data clearly show a decreased ACKR2 mRNA expression on PBMCs and increased plasma IL-33 levels of patients with MS. There was no significant relationship between ACKR2 and other cytokine levels. Within our knowledge, this is the first study that evaluates the ACKR2 mRNA expression in the PBMCs of MS patients.

Keywords: Atypical chemokine receptor 2 (ACKR2); Cytokines; Immunopathogenesis; Inflammation; Interleukin-33 (IL-33); Multiple sclerosis (MS).

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Female
  • Humans
  • Inflammation / blood*
  • Interleukin-33 / blood*
  • Interleukin-6 / blood
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Prospective Studies
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / blood*
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • ACKR2 protein, human
  • IL33 protein, human
  • IL6 protein, human
  • Interleukin-33
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Chemokine
  • TNF protein, human
  • Tumor Necrosis Factor-alpha