Researchers have found that cigarette smoking can induce colitis in mice through specific immune cell response.
The study “Cigarette Smoking Triggers Colitis by IFN-γ+ CD4+ T Cells,” was published in the journal Frontiers in Immunology.
Multiple epidemiological and clinical studies have indicated a potential link between cigarette smoking and the development of colitis. In fact, cigarette smoking has been shown to be the strongest risk factor contributing to Crohn’s disease, as the incidence of Crohn’s is much higher in patients with airway diseases.
However, despite the prior establishment of a link between cigarette smoke and Crohn’s disease, few laboratory studies have been conducted to determine how cigarette smoking leads to the condition. So, researchers at Kyung Hee University set out to explore the relationship.
The cellular immune response is carried by multiple cell types, which includes two types of T-cells known as Th1 and Th17 cells. IFN-γ is a molecule that is expressed by these immune cells and has been shown to play a role in immunity, including autoimmunity. In fact, IFN-γ has been shown to be over-produced in many gastric diseases, including Crohn’s disease. Furthermore, levels of IFN-γ also have been shown to increase after cigarette smoke exposure. That’s why researchers hypothesized that cigarette smoke was increasing the risk of Crohn’s disease through expression of IFN-γ.
First, researchers demonstrated that cigarette smoke exposure in mice led to the typical characteristics of colitis, including shorter colon length, reduced body weight, infiltration of inflammatory cells and colon mucous thickening.
Then, when assaying for the types of immune cells that were expressed in mice after cigarette exposure, they determined that Th1 cells were increased, but not Th17 cells. This indicated that cigarette exposure causes colitis through a Th1-immune cell response.
Subsequently, the researchers demonstrated that when mice were depleted of CD4+ T-cells (a type of Th1 cell), they were protected against colitis induced by cigarette smoke. Furthermore, when the T-bet gene, which leads to the expression of IFN-γ, was knocked out (deleted), the lack of IFN-γ also was sufficient to protect against the development of colitis. This indicates that CD4+ T-cells carried out this response through IFN-γ.
Researchers then showed that transferring T-cells from mice that were exposed to cigarette smoke to mice that were prone to develop colitis caused the latter group of “knock-out” mice did not cause colitis.
Thus, the authors conclude, “Our findings identify a novel mechanism of CS-induced colitis: the mediation of immune activation via T-bet/IFN-γ-mediated CD4+ T cells. IFN-γ plays a substantial role in colitis induced by CS exposure.”
“An understanding of the T-bet/IFN-γ-mediated CD4+ T cell changes in the colon extends our understanding of CS-induced pathology, which may result in the development of novel therapeutic strategies to treat Crohn’s disease,” the authors added.
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