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Dendritic Cells: A Prime Suspect in Crohn's Disease

Jun 16, 2014 1:00:44 PM / by Daisy

Dendritic cells are the suspect in Crohn's disease. It is also thought that dendritic cells isolated from PBMCs can be manipulated to cure Crohn's disease.

Common estimates are that we harbor somewhere between 300 to 1000 different species of bacteria in our gut. These bacteria are harmless and many aid in the digestion of food. But our bodies are wired to identify and eradicate bacteria. So, to accommodate our gut bacteria, a specialized network of peripheral blood mononuclear cells (PBMCs) live in the gut, specifically in the mucosa, to maintain tolerance and make peace with these tenants.

dendritic cells Dendritic cells are thought to be the suspect in Crohn's disease which affects the gastrointestinal tract. Image credit:l-glutaminetruth.com

In spite of the sophisticated arrangements to tolerate gut bacteria,  communication sometimes breaks down. This results in PBMCs traveling out of the blood and to the intestine to cause inflammation. Inflammation causes localized pain, redness, and the release of chemical signals (histamines and cytokines) by PBMCs to broadcast danger and recruit more PBMCs.  When inflammation persists long term in the gut, it can develop into irritable bowel disease (IBD). Crohn's disease is a certain form of IBD. Crohn's patients report diarrhea and cramping, and surgery is sometimes necessary to remove or repair damaged tissue.

Defective dendritic cells are suspect in several disorders, including the Crohn's disease. Dendritic cells constantly sample the environment. In the body, they pass on the signal from bacteria to PBMCs to mount an immune response. In the gut, they pass on signals to PBMCs to get a tolerance response. Scientists use markers present on the cell surface to identify classes of dendritic cells, including those from the gut mucosa. In humans, dendritic cells with the CD103+ marker are the ones that promote tolerance and are associated with the gut mucosa.

In a recent review [1], the authors discuss an approach to generate tolerant dendritic cells. Further, they developed a protocol to treat Crohn's disease patients by producing such cells under clinical grade conditions. The crucial discovery that enabled this procedure was learning that the disease does not eliminate the inherent ability of dendritic cells to become tolerant dendritic cells. Scientists isolated monocytes (a precursor to dendritic cells) from PBMCs from Crohn's patients. The monocytes were cultured in the lab with a cocktail that promoted their differentiation into tolerant dendritic cells. This protocol can now be tested further for efficacy (usefulness) in the patient.

HemaCare is a provider of dendritic cells for research purposes. HemaCare also provides disease-state products such as PBMCs from Crohn's disease patients to enable research for the cure of Crohn's disease.

Reference:

[1]. Cabezón R, Benítez-Ribas D. Therapeutic potential of tolerogenic dendritic cells in IBD: from animal models to clinical application. Clin Dev Immunol. 2013;2013:789814. PubMed PMID: 24319468; PubMed Central PMCID: PMC3844279.

 

Topics: crohn's disease, Dendritic Cells, PBMCs, Basic Research

Daisy

Written by Daisy

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