Smoking-induced autoimmunity

Smoking-induced autoimmunity

Cigarette smoking has been linked to risk of disease or to disease phenotype in a number of autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis. The local microenvironment, such as that present in the lung, may determine which antigens are presented, and also direct the alternative fates of effector and regulatory T cell subsets and macrophages. However, very little is known about the influence of smoking in this regard, and how it may lead to autoimmunity.

Healthy non-smokers, smokers with normal lung function and patients (see above) are included in our studies. Samples are obtained from peripheral blood and from the deep airways by means of bronchoscopy with bronchoalveolar lavage (BAL).

Characterization of effector and regulatory T cell populations and other leukocyte subsets are done by antibody surface staining as well as intracellular staining for select combinations of cytokines and transcription factors, followed by multicolor flow cytometry. Auto-antigenic peptides presented by HLA-DR molecules on BAL cells will be identified by mass spectrometry, followed by screening for T cell responses by e.g. ELISPOT assay and flow cytometry for intracellular cytokines. Macrophage polarization is studied, and inflammasome activation and TLR signaling in monocytes and alveolar macrophages are evaluated ex vivo and after in vitro stimulation with select ligands.

Our overall aim is to find immune mechanisms induced in the lungs after cigarette smoke exposure, and that may be common for antigen-specific inflammatory diseases initiated in the lungs. The knowledge gained should provide a rational basis for novel therapeutic strategies

 

GruppChefPortlet

Team leader

Johan Öckinger

E-mail

johan.ockinger@ki.se

Job title

Assistant professor

House

BioClinicum J7:30