RGD Reference Report - Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production. - Rat Genome Database

RGD Reference Report - Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production. - Rat Genome Database

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Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production.
Authors:	Yu, SL Wong, CK Wong, PT Chen, DP Szeto, CC Li, EK Tam, LS
Citation:	Yu SL, etal., PLoS One. 2011;6(8):e23855. Epub 2011 Aug 19.
RGD ID:	5508746
Pubmed:	PMID:21886831 (View Abstract at PubMed)
PMCID:	PMC3158772 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.pone.0023855 (Journal Full-text)
BACKGROUND: Pattern recognition receptors (PRRs) such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients, for playing immunopathological roles. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the expression and function of the PRR nucleotide-binding oligomerization domain (NOD2) in SLE. NOD2 expression in T, B lymphocytes, monocytes, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) was assessed in SLE patients and healthy controls (HCs) using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon NOD2 agonist muramyl dipeptide (MDP) stimulation was assessed using Cytometric Bead Array. Over-expression of NOD2 in monocytes was observed in immunosuppressant naive SLE patients, and was positively associated with longer disease duration. Immunosuppressive therapy was an independent explanatory variable for downregulating NOD2 expression in CD8+ T, monocytes, mDCs and pDCs. Ex vivo basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly increased in immunosuppressant naive patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (%) of cytokines (IL-1beta) from PBMC was significantly increased in immunosuppressant naive patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (%) of IL-10 in patients with inactive disease compared with immunosuppressant naive patients and HCs. CONCLUSIONS/SIGNIFICANCE: Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naive SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the immunopathological mechanisms in SLE. Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes, monocytes, and DCs in SLE patients which subsequently IL-10 reduction, contributing towards the regulation of immunopathological mechanisms of SLE, at the expense of increasing risk of bacterial infection.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
NOD2	Human	systemic lupus erythematosus		IEP		protein:increased expression:monocyte	RGD
Nod2	Rat	systemic lupus erythematosus		ISO	NOD2 (Homo sapiens)	protein:increased expression:monocyte	RGD
Nod2	Mouse	systemic lupus erythematosus		ISO	NOD2 (Homo sapiens)	protein:increased expression:monocyte	RGD

Genes (Rattus norvegicus)


Nod2 (nucleotide-binding oligomerization domain containing 2)

Genes (Mus musculus)


Nod2 (nucleotide-binding oligomerization domain containing 2)

Genes (Homo sapiens)


NOD2 (nucleotide binding oligomerization domain containing 2)