Activation status of mucosal-associated invariant T cells reflects disease activity and pathology of systemic lupus erythematosusReportar como inadecuado




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Arthritis Research and Therapy

, 19:58

First Online: 14 March 2017Received: 28 October 2016Accepted: 10 February 2017

Abstract

BackgroundMucosal-associated invariant T MAIT cells are innate-like lymphocytes constituting a large proportion of peripheral blood T cells expressing αβ T-cell receptor in humans. In this study, we aimed to investigate their involvement in systemic lupus erythematosus SLE.

MethodsPeripheral blood MAIT cells from patients with SLE were assessed for their frequency, activation markers, and cell death by flow cytometry. The correlation between plasma cytokine levels and CD69 expression on MAIT cells was analyzed. The major histocompatibility complex class I-related protein MR1-restricted antigen-presenting capacity of antigen-presenting cells was investigated. Cytokine-mediated activation of MAIT cells in the absence of exogenous antigens was also examined.

ResultsThe frequency of MAIT cells was markedly reduced in SLE. The reduced number of MAIT cells was not attributable to the downregulation of surface markers, but it was partially due to the enhanced cell death of MAIT cells, possibly by activation-induced cell death. The CD69 expression levels on MAIT cells in SLE correlated with disease activity. Moreover, monocytes from patients with SLE exhibited increased ability to induce MAIT cell activation. The plasma concentration of interleukin IL-6, IL-18, and interferon IFN-α positively correlated with the expression levels of CD69 on MAIT cells in SLE. MAIT cells were activated by cytokines, including IFN-α, IL-15, and IL-12 plus IL-18, in the absence of exogenous antigens.

ConclusionsThese results suggest that MAIT cells reflect the pathological condition of SLE and that their activated status correlates with presence of disease.

KeywordsSystemic lupus erythematosus Innate-like lymphocytes Mucosal-associated invariant T cells Activation marker Disease activity index Antigen presentation Cytokines Abbreviations7-AAD7-Aminoactinomycin D

APCAllophycocyanin

CCRC-C chemokine receptor

Cy5.5Cyanine 5.5

FACSFluorescence-activated cell sorting

FITCFluorescein isothiocyanate

GM-CSFGranulocyte-macrophage colony-stimulating factor

HCHealthy control subject

IFN-αInterferon-α

ILInterleukin

iNKTInvariant natural killer T cells

mAbMonoclonal antibody

MAITMucosal-associated invariant T cells

MFIMean fluorescence intensity

MR1Major histocompatibility complex class I-related protein

MR1LMajor histocompatibility complex class I-related protein ligand

NKNatural killer cells

PBMCPeripheral blood mononuclear cell

PD-1Programmed cell death protein 1

PEPhycoerythrin

PerCPPeridinin chlorophyll

RT-PCRReverse transcriptase-polymerase chain reaction

SLESystemic lupus erythematosus

SLEDAISystemic Lupus Erythematosus Disease Activity Index

TCRT-cell receptor

TNF-αTumor necrosis factor-α

VCAM-1Vascular cell adhesion molecule-1

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Autor: Asako Chiba - Naoto Tamura - Kazunori Yoshikiyo - Goh Murayama - Mie Kitagaichi - Ken Yamaji - Yoshinari Takasaki - Sachiko

Fuente: https://link.springer.com/







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