NOD1 Engagement Leads to Increased IL12/IL23 p40 and decreased IL-10 Expressions in Sarcoidosis as Compared to Healthy Subjects (98.17)

Abstract

Abstract Sarcoidosis is a systemic inflammatory disorder of unknown etiology affecting barrier organs like lung and skin. The presence of granuloma and its associated inflammation may lead to organ dysfunction. Two NLR family members, NOD1 and NOD2, trigger immune defenses in response to bacterial peptidoglycans (PGNs). Interaction between these sensors and microbial moieties leads to up-regulation of cytokines involved in innate and adaptive immunity. We hypothesize that granuloma formation in sarcoidosis is due to an abnormal sensing of specific microbial constituents through NOD1, leading to an aberrant induction of pro-inflammatory and/or a decreased anti-inflammatory cytokines. Methods: We assessed the functional responses of whole blood or isolated PBMC of patients with established diagnosis of sarcoidosis in response to NOD1 and TLR agonists and compared to those of healthy subjects. Pro- and anti-inflammatory cytokines were measured at the gene and protein levels. Our results demonstrate that subjects with sarcoidosis expressed several cytokines including IL-1β, IL-8 and IL-6 significantly higher at baseline as compared to healthy controls. Secondly we show for the first time that patients with sarcoidosis respond to NOD1 stimulation and to co-stimulation of NOD1 and TLR4 receptors with a significant increase of IL12/IL23 p40 and decrease of IL-10 expressions at both the gene and protein levels.