Th17 cells

[Guest guest]

Dear All;

This recent article explains why immunologists should be excited

about Th17 cells (a newly discovered set of T cells that can cause

inflammation), their involvement in inflammatory bowel diseases, and

how to block them:

_______________________

Inflammatory Bowel Diseases - Published Online: 2 May 2007

Il-6 signaling in inflammatory bowel disease: pathophysiological role

and clinical relevance.

Jonas Mudter, MD, Markus F. Neurath, MD

1st Medical Clinic, Johannes Gutenberg University of Mainz, Germany

Keywords

inflammatory bowel disease • IL-6 • IL-17 • trans signaling • colitis

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are chronic

inflammatory bowel diseases (IBDs) occurring in the gut of

genetically susceptible individuals independent of a specific

pathogen. The interaction between antigen-presenting cells and the

local bacterial flora contributes to an uncontrolled activation of

mucosal CD4+ T lymphocytes with the consecutive release of

proinflammatory cytokines such as tumor necrosis factor (TNF),

interleukin (IL)-6, IL-12, IL-23, IL-27, and also IL-17, which is

attributed to a specific, differentiated CD4+ lineage called Th17 (TH-

IL17, THi). Recent data suggest that IL-6 contributes to Th17

differentiation. However, to clarify the importance of Th17 cells in

IBD further data are needed. So far, CD has been attributed to a Th1-

mediated disease, whereas UC exhibits a modified Th2 cytokine

response. In both diseases CD4+ T cells at the site of inflammation

are critically dependent on antiapoptotic IL-6 signaling. Thereby, IL-

6 induces the transcription factor STAT-3 via transsignaling

(activation of a cell lacking membrane-bound IL-6 receptor via

soluble IL-6 receptor). STAT-3 itself induces the antiapoptotic

factors bcl-2 and bcl-xL, thus resulting in T-cell resistance against

apoptosis. This vicious circle of T-cell accumulation, mediated by

apoptosis resistance, finally leading to chronic inflammation, can be

blocked by anti-IL-6 receptor antibodies. This review highlights the

role of IL-6 in IBD immunopathogenesis and its clinical relevance in

IBD therapy and diagnostics.

__________________

I'll try to write an article on these Th17 cells for the next

newsletter. I hope that PSC researchers will start taking a close

look at them too!

Can anyone get a copy of this article?

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)