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Targeting T Cells to Treat IBD

Sep 4, 2018 10:05:00 AM / by Stacy Matthews Branch, DVM, PhD

The woman wake up for go to restroom. People with diarrhea problem concept_AdobeStock_163356958-161483-editedRecent research looks into the relationship between T helper cells and the autoimmune conditions of inflammatory bowel disease (IBD).

Crohn’s disease and ulcerative colitis are two forms of inflammatory bowel disease (IBD) caused by an immune dysfunction. People with IBD can experience diarrhea, rectal bleeding, constipation, abdominal pain and cramping, fatigue, loss of appetite, and weight loss. Dysregulated responses of a subset of CD4 T cells (T helper cells) are associated with autoimmune and chronic inflammatory conditions and may induce and maintain intestinal inflammation, but the mechanism is not fully understood. The primary cytokine secreted by T helper cells of the intestinal mucosa of people with IBD is interferon (IFN)-gamma. Recent research was conducted to better understand the role of IFN-producing CD4 T cells in the initiation and maintenance of IBD.

The research involved the use of a mouse model of colitis and the isolation of IFN-gamma-producing and nonproducing CD4 T cells from the spleens and lymph nodes of the mice. These cells were then transferred to disease-free mice. Although IFN-gamma has proinflammatory properties, the IFN-gamma-producing CD4 T cells only caused mild disease in the mice after cell transfer, but the IFN-gamma-nonproducing cells caused significant epithelial damage and intestinal inflammation.

Another curious finding was the stem-like or progenitor-cell features of the pathogenic subset of CD4 T cells. RNA sequencing and analysis of transcripts from the IFN-gamma producing and nonproducing cells have a stem cell–like transcriptional profile, including increased expression of molecules essential for cell self-renewal. The IFN-gamma–nonproducing CD4 T cells also appear to be less susceptible to apoptosis given their higher numbers compared to the IFN-producing cells after transfer to the disease-free mice. In addition, the IFN-gamma–nonproducing CD4 T cells had higher mitochondrial reserve capacity (also associated with stemness) than the IFN-gamma producing cells.

Overall, the results of the study demonstrate the association of an IFN-nonproducing subset of stem-like CD4 T cells with the pathogenesis and maintenance of intestinal inflammatory conditions. The new information obtained from these results may be used to study the role of this subset of CD4 T cells in other chronic inflammatory and autoimmune disorders. The distinct population of CD4 T cells may also serve as targets for newly designed therapies to treat or cure IBD and other conditions.

Check out HemaCare’s supply of T cells, along with other human cells and tissues, to use in your research of IBD and other medical conditions.

Reference:

PhD, C. (2018). Could treating these immune cells cure IBD?. Medical News Today. Retrieved 23 July 2018, from https://www.medicalnewstoday.com/articles/322299.php

Topics: CD4+ T cells, T helper cells, autoimmune disease, autoimmune disorder

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