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pr40

one autoimmune mechanism uncovered

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PR40,

 

When I read the article that you linked, I noticed this one as I started clicking around that site. Thanks for posting.

 

http://www.medicalnewstoday.com/articles/152822.php?trendmd-shared=0

Hydrangea Root Shows Promise In Treating Autoimmune Disorders

 

An exciting new area in the field of autoimmune disease research is learning about the role of a particular immune system cell called the T helper 17 (Th17) which is genetically different from other types of CD4+ T cell like the Th1, Th2 and T-regulatory cells and appears to play a unique role in the part of the immune system that causes harm when it over-reacts.

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The plot thickens on TH17 Resistant to steroids/ this type found in Crohn's/ interesting stuff/bolding mine

 

http://jem.rupress.org/content/211/1/89.long

Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids

 

IL-17A–expressing CD4+ T cells (Th17 cells) are generally regarded as key effectors of autoimmune inflammation. However, not all Th17 cells are pro-inflammatory. Pathogenic Th17 cells that induce autoimmunity in mice are distinguished from nonpathogenic Th17 cells by a unique transcriptional signature, including high Il23r expression, and these cells require Il23r for their inflammatory function. In contrast, defining features of human pro-inflammatory Th17 cells are unknown. We show that pro-inflammatory human Th17 cells are restricted to a subset of CCR6+CXCR3hiCCR4loCCR10CD161+ cells that transiently express c-Kit and stably express P-glycoprotein (P-gp)/multi-drug resistance type 1 (MDR1). In contrast to MDR1 Th1 or Th17 cells, MDR1+ Th17 cells produce both Th17 (IL-17A, IL-17F, and IL-22) and Th1 (IFN-γ) cytokines upon TCR stimulation and do not express IL-10 or other anti-inflammatory molecules. These cells also display a transcriptional signature akin to pathogenic mouse Th17 cells and show heightened functional responses to IL-23 stimulation. In vivo, MDR1+ Th17 cells are enriched and activated in the gut of Crohn’s disease patients. Furthermore, MDR1+ Th17 cells are refractory to several glucocorticoids used to treat clinical autoimmune disease. Thus, MDR1+ Th17 cells may be important mediators of chronic inflammation, particularly in clinical settings of steroid resistant inflammatory disease.

Edited by kim

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PR40,

 

When I read the article that you linked, I noticed this one as I started clicking around that site. Thanks for posting.

 

http://www.medicalnewstoday.com/articles/152822.php?trendmd-shared=0

Hydrangea Root Shows Promise In Treating Autoimmune Disorders

 

An exciting new area in the field of autoimmune disease research is learning about the role of a particular immune system cell called the T helper 17 (Th17) which is genetically different from other types of CD4+ T cell like the Th1, Th2 and T-regulatory cells and appears to play a unique role in the part of the immune system that causes harm when it over-reacts.

 

A quick search shows that hydrangea root is typically used for breaking up the mineral deposits of kidney stones. I'm trying to find out more on its interaction with Ca2+, if any.

 

There are a number of pubmed articles on halofuginone though perhaps in the context of other sources besides hydrangea. E.g., for malaria and toxoplasmosis, various cancers, muscular dystrophy, leukemia. An interesting rabbit trail!

Edited by jan251

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Jan,

 

I was wondering if the kids who don't show a response to steroids and seem not to respond or have a lot of problems with phama drugs/antibiotics, are in fact signaling a problem with this type of TH response. MDR1 function is something I would like to take a closer look at.

 

More hours in a day please,lol.

 

Here, we report that high-level IL23R expression within human memory T cells is restricted to a subset of CCR6+CXCR3hiCCR4loCCR10CD161+ cells that selectively expresses the multi-drug transporter MDR1 (also known as P-glycoprotein [P-gp] and ABCB1). MDR1 is an ATP-dependent membrane efflux pump with broad substrate specificity best known for its role in promoting tumor resistance to chemotherapy (Gottesman et al., 2002). In nonmalignant cells, MDR1 is expressed on intestinal epithelium, endothelial cells of the blood-brain-barrier, and hepatocytes, where it controls the accumulation of xenobiotic compounds and exogenous pharmacologic molecules (Schinkel, 1997). MDR1 is also expressed in progenitor cell types, and is thought to play a role in the survival and longevity of these cells (Chaudhary and Roninson, 1991; Sincock and Ashman, 1997). Consistent with this, we show that a sizeable proportion of human MDR1+ Th17 cells also express the stem cell marker c-Kit. All c-Kit+ memory T cells display robust MDR1 activity, and these cells give rise to c-KitMDR1+ progeny after inflammatory T cell activation in the presence of IL-23. Both c-Kit+ and c-Kit MDR1+ Th17 cells display unique pro-inflammatory characteristics, including production of Th17 and Th1 cytokines, reduced expression of IL-10 and other anti-inflammatory molecules, and hypersensitivity to IL-23 stimulation, where they display enhanced activation of STAT3 and marked up-regulation of IL-17A compared with MDR1 memory T cell subsets.

Importantly, we show that c-KitCD161+MDR1+ Th17 cells are enriched and activated in CD patient lesions, and that MDR1+ Th17 cells are uniquely resistant to the anti-inflammatory actions of several glucocorticoids used to treat CD and other clinical autoimmune syndromes. Thus, MDR1 is a unique feature of pro-inflammatory and steroid-resistant Th17 cells in humans, which may be exploited to improve the diagnosis, characterization, and treatment of patients with chronic and steroid-resistant inflammatory diseases.

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