Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Hi , Thank you so much for taking the time to write that explanation! I really appreciate it and I know everyone else does too. You are very gifted in your understanding of this topic and the technical terms associated with them. I am sure some of it is due to your passion in this subject. Thanks again!! Lori A. "Aggressively Pursuing Solutions To Your Real Estate Needs!" First Weber Group Cell: 1507 E. Sunset Drive Waukesha, WI 53189 LoriUSA@... www.Lori.FirstWeber.com Re: New PSC leads Hi Lori;I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes ....In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the "zip-code" imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this "zip-code" imprinting system or mail delivery system? A disgruntled postal worker?The interesting new "lead" is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address!Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC?The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs).Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs.Best regards,Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Thank you for that outstanding explanation! Even I can understand what that complex study was about. Blessings, Barby Quote Link to comment Share on other sites More sharing options...
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