RE: Th17 versus Treg balance: a unifying hypothesis about IBD?

March 2, 2009

Dave,

This is fascinating! Thank you so much for posting this

and making it understandable. We are SO blessed to have you!

Together in the fight…Whatever it takes!

Joanne (mom of Todd, 22, PSC 01, Crohns 02, TX Twice 03, rPSC

05, Diabetes 06, AIH overlap 08 & living life to the fullest 09)

March 2, 2009

Hi Joanne;

I worry that this is getting so complicated that it's getting hard to explain. But I do think that the Th17 cell versus Treg balance issue is an important one for IBD. I wish I could extend it to PSC, but there is only fragmentary information so far.

In PBC there does seem to be an involvement of pro-inflammatory Th17 cells that infiltrate the liver, causing inflammation:

http://www.ncbi.nlm.nih.gov/pubmed/19101114

The mice used as the animal model in these studies are Treg-deficient, and they spontaneously develop PBC:

http://www.ncbi.nlm.nih.gov/pubmed/17058261

So, in PBC there definitely seems to be an imbalance between Tregs and Th17 cells!

I hope this will be looked at in PSC soon.

Best regards,

Dave R.

March 2, 2009

Hi Joanne;

I worry that this is getting so complicated that it's getting hard to explain. But I do think that the Th17 cell versus Treg balance issue is an important one for IBD. I wish I could extend it to PSC, but there is only fragmentary information so far.

In PBC there does seem to be an involvement of pro-inflammatory Th17 cells that infiltrate the liver, causing inflammation:

http://www.ncbi.nlm.nih.gov/pubmed/19101114

The mice used as the animal model in these studies are Treg-deficient, and they spontaneously develop PBC:

http://www.ncbi.nlm.nih.gov/pubmed/17058261

So, in PBC there definitely seems to be an imbalance between Tregs and Th17 cells!

I hope this will be looked at in PSC soon.

Best regards,

Dave R.

March 2, 2009

Hi Joanne;

I worry that this is getting so complicated that it's getting hard to explain. But I do think that the Th17 cell versus Treg balance issue is an important one for IBD. I wish I could extend it to PSC, but there is only fragmentary information so far.

In PBC there does seem to be an involvement of pro-inflammatory Th17 cells that infiltrate the liver, causing inflammation:

http://www.ncbi.nlm.nih.gov/pubmed/19101114

The mice used as the animal model in these studies are Treg-deficient, and they spontaneously develop PBC:

http://www.ncbi.nlm.nih.gov/pubmed/17058261

So, in PBC there definitely seems to be an imbalance between Tregs and Th17 cells!

I hope this will be looked at in PSC soon.

Best regards,

Dave R.

March 2, 2009

Joanne;

I also want to stress that I'm not the only one talking about this:

Pediatr Res. Feb 11 [Epub ahead of print](2009)

The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity.

Eisenstein EM, CB

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI

53226.

Regulatory T cells and T helper 17 cells are two recently described

lymphocyte subsets with opposing actions. In this review, we discuss

the mechanisms that promote development of these cells from common

precursors and the specific factors that impact their cell numbers

and function. Altered regulation of this key developmental checkpoint

may contribute to the pathophysiology of autoimmune diseases by

tipping the balance toward inflammation. We also present recent

findings that suggest how the equilibrium between regulatory T cells

and pro-inflammatory T helper subsets might be pharmacologically

restored for therapeutic benefit. PMID: 19218879.

Dave R.

March 2, 2009