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AB0104 Modulation of immunity through cigarette smoke induced changes in dendritic cell functions - potential relevance to autoimmunity
  1. R. Vassallo1,
  2. P. Walters1,
  3. V. Taneja2
  1. 1Pulmonary and Critical Care Medicine
  2. 2Immunology, MAYO CLINIC, Rochester, Minnesota, United States

Abstract

Background Epidemiological studies implicate cigarette smoking as a major risk factor predisposing to the development of seropositive rheumatoid arthritis (RA). The mechanisms by which cigarette smoking promotes RA are largely unknown, but likely involve modulation of dendritic cell (DC) functions.

Objectives To determine mechanisms by which cigarette smoke modulates DC functions thereby potentially modulating antigen presentation and promoting autoimmunity.

Methods C57B6 mice were placed in a TE-2 smoking chamber and chronically exposed to cigarette smoke generated from Kentucky 3R4F research cigarettes. Murine DCs were extracted from the spleen and lymph nodes at the time of sacrifice, and analyzed for viability, T cell proliferative potential, and cytokine/chemokine secretion. Bone marrow DCs were stimulated with lipopolysaccharide in the presence or absence of cigarette smoke extract and microarray analysis performed to determine alternations in gene expression induced by cigarette smoke.

Results DCs extracted from cigarette smoke exposed mice demonstrated enhanced viability and minor alteration in costimulatory molecule expression. DC-mediated allo-proliferative T cell responses were not significantly different between cigarette smoke exposed and control DCs. LPS-activated DC extracted from cigarette smoke exposed mice produced lower amounts of interleukin-12, but produced greater amounts of TNF-alpha, PGE2, and neutrophilic chemokines. Gene array analysis of DCs incubated with cigarette smoke extract during activation with LPS showed augmentation and suppression of a large number of genes associated with cellular toxicity, oxidative stress, and immune regulation.

Conclusions Cigarette smoke exposure modifies murine DC functions in profound ways. The effect of smoking on host DC function is complex and both stimulatory and suppressive effects occur. The determination of specific cigarette smoke induced effects on DC functions, and the determination of cigarette smoke effects on antigen-specific immunity, particularly in the context of specific host genetic traits, are essential future studies needed to clarify specific mechanisms by which smoking promotes seropositive RA.

Disclosure of Interest None Declared

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