Inflammatory bowel disease (IBD) is a defined as inflammation of the intestines. It comes in two forms: 1) Crohn’s disease (CD) which causes lesions in the entire wall of the bowel and 2) ulcerative colitis (UC) which is characterized as inflammation in the mucosal layer of the colon (hope this did not gross anyone out too much…). Surprisingly though, the symptoms associated with IBD is NOT caused by a particular pathogen, but by the attack of one’s own immune system. Therefore, IBS is characterized as an autoimmune disease. Microbial translocation, where microbial products enter systematic circulation due to loss of barrier integrity of the intestines, has also been observed in IBD, as well as other disorders. Although great strides have been made to the understanding of IBD, the roles of specific immune cells types are still not completely clear. In order to better understand IBD, Funderburg et al. (2013) studied if the accompanying inflammation is linked to T-cell activation and thus microbial translocation.
Funderburg et al. found several important results. First, blood plasma samples were taken in individuals with IBD and soluble inflammatory markers were measured. CRP (a protein found in the blood during inflammation) and IL-6 (pro-inflammatory cytokine) levels both increased in IBD patients, which is not surprising because IBD is characterized by inflammation.
Inflamed Colonic Tissue
Second, T cell levels were measured using flow cytometry (a fancy device that uses a laser to count/sort cells). Both the proportions of activated CD8+ T cells and (CD38+ HLA-DR+) CD4+ T cells increased in patients with IBD. CD8+ T cells are cytotoxic and triggers apoptosis (cell death) in infected cells while CD38+ (adhesion molecule) HLA-DR+ (MHC class II receptor) CD4+ T cells are “helpers,” which assist in activating cytotoxic T cells, cause Ab-class switching, and macrophage activation. These results indicate a possible link between systemic inflammation and T-cell activation. It is also important to note that T cells in patients with IBD are more likely to have recently entered into the cell cycle, which is indicated by the expression of intracellular Ki-67 (nuclear protein associated with proliferation).
Third, plasma levels of LBP (presents bacterial lipopolysaccharides to PRRs) increase in patients with active IBD, which could indicate microbial translocation and contribute to LBS clearance.
Overall, these results suggest inflammation and damage in the intestines in patients with IBD might be a result of T cell activation and previous exposure of LBS or other microbial products consistent with the gastrointestinal lumen (I would like to note that although I find the results of this paper more or less strong, I do not know why T cell activation is not a result of IBD, and not visa versa).
So why should you care about an inflamed colon? Well, Other autoimmune diseases and pathogenic problems related to over inflammation show similar increase in pro-inflammatory markers and cytokine levels, suggesting similar effector functions, disease symptoms, and therefore possible treatments. Overall, to better understand how to cure a disease or treat a symptom, you need to understand the pathogenic or immune response cause.
Funderburg, Nicholas et al. Circulating CD4(+) and CD8(+) T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation. September 2013. Immunology. 140(1): 87-97.
Mak, Tak W. & Saunders, Mary E. (2011) Primer to the Immune Response. Burlington, MA: AP Cell.
Podolsky, Daniel. Inflammatory Bowel Disease. 26 September 1991. N Engl J Med. 325(1): 928-937.