The Th17 lineage : a new arm of adaptive immunity

[Guest guest]

Dear All;

The other day I posted an article on the genetics of inflammatory

bowel disease, which discusses the growing evidence that Th17 cells

are involved in this disease:

Cho JH, Weaver CT (2007) The genetics of inflammatory bowel

disease. Gastroenterology 133: 1327-1339.

One of the authors of this study is Casey Weaver. He and his

colleagues have done a lot of the recent work on characterizing this

new Th17 cell lineage, and if you'd like to learn more about these

cells and how they were discovered, I can recommend this video of a

seminar he gave in May 2007:

https://videocast.nih.gov/Summary.asp?File=13824

The Th17 lineage : a new arm of adaptive immunity / Casey Weaver

I'm sure you'll be hearing much more about these cells in the future.

For example, this recent paper shows that interleukin-21 (IL-21)

promotes Th17 cell development at the expense of regulatory T cells

(Tregs), an effect that may be opposite to that of retinoic acid

(which stimulates Tregs at the expense of Th17 cells):

Eur J Immunol. 2007 Oct 4; [Epub ahead of print]

IL-21 regulates experimental colitis by modulating the balance

between T(reg) and Th17 cells.

Fantini MC, Rizzo A, Fina D, Caruso R, Becker C, Neurath MF,

Macdonald TT, Pallone F, Monteleone G

Division of Gastroenterology, University of Rome Tor Vergata, Rome,

Italy.

Regulatory T (T(reg)) cells play a key role in the maintenance of the

immune system homeostasis. T(reg) cells can be generated in the

periphery under control of TGF-beta, a cytokine involved in the

negative control of the immune system. However, TGF-beta cooperates

with IL-6 in the generation of Th17 cells, a novel class of effector

cells involved in numerous inflammatory diseases, including colitis.

Therefore, TGF-beta emerges as a mediator of both anti-inflammatory

and pro-inflammatory processes, depending on the local cytokine

milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by

T cells and involved in the pathogenesis of immune-mediated diseases,

prevents the TGF-beta-dependent expression of FoxP3, the master

regulator of T(reg) cell commitment, and the induction of suppressive

capacity in naive CD4(+) T cells, while promoting the differentiation

of Th17 cells. In vivo, CD4(+) naive T cells activated in the

presence of TGF-beta and IL-21 failed to suppress colitis while

inducing an inflammatory response characterized by high levels of IL-

17 and RORgammat, the transcription factor expressed by Th17 cells.

Therefore, IL-21 emerges as a key modulator of TGF-beta signaling,

leading to the reciprocal differentiation of T(reg) and Th17 cells.

PMID: 17918200

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)