Th17 cells in Primary Biliary Cirrhosis

[Guest guest]

Dear All;

Since early 2007 I've been interested in new developments in

immunology which indicate that a recently discovered set of T cells

are major players in autoimmune diseases ... Th17 cells that produce

the inflammatory cytokine, interleukin-17 (IL-17). These Th17 cells

have since been shown to be involved in inflammatory bowel disease,

psoriasis, rheumatoid arthritis, multiple sclerosis, uveitis and

scleritis (to name but a few autoimmine (autoinflammatory) diseases).

There has been nothing published about them in PSC yet, but hopefully

this report on primary biliary cirrhosis (PBC) will generate some

interest:

J. Autoimmun. Dec 18 [Epub ahead of print](2008)

Hepatic IL-17 responses in human and murine primary biliary cirrhosis.

Lan RY, Salunga TL, Tsuneyama K, Lian ZX, Yang GX, Hsu W, Moritoki Y,

Ansari AA, Kemper C, Price J, Atkinson JP, Coppel RL, Gershwin M

Division of Rheumatology, Allergy and Clinical Immunology, Genome and

Biomedical Sciences Facility, University of California at , 451

East Health Sciences Drive, Suite 6510, , CA 95616, USA.

The emergence of new regulatory and pro-inflammatory immune cell

subsets and cytokines dictates the need to re-examine the role of

these subsets in various diseases involving the immune system. IL-17

has been recently identified as a key cytokine involved in numerous

autoimmune processes. However, its role in liver autoimmune diseases

remains unclear. Primary biliary cirrhosis (PBC) is characterized

histologically by autoreactive CD4 and CD8 T cells surrounding

damaged bile ducts. CD4(+) T cells are a major source of IL-17, which

compose a distinct T helper subset (Th17). Thus we set out to

determine the role of IL-17 in both human and a murine model of PBC

in a liver-targeted manner. Our data demonstrate an increase in the

frequency of IL-17(+) lymphocytic infiltration in liver tissues from

PBC patients and those with other liver dysfunctions as compared to

healthy livers. IL-2 receptor alpha knockout mice, a recently

identified murine model of human PBC, also demonstrate marked

aggregations of IL-17-positive cells within portal tracts and

increased frequencies of Th17 cells in the liver compared to the

periphery. Interestingly, CD4(+) T cells from livers of normal

C57BL/6J mice also secreted higher levels of IL-17 relative to those

from spleens, indicating a preferential induction of Th17 cells in

liver tissues. Importantly, C57BL/6J cocultures of splenic CD4(+) T

cells and liver non-parenchymal cells increased IL-17 production

approximately 10-fold compared to T cells alone, suggesting a role of

the liver microenvironment in Th17 induction in cases of liver

autoimmunity and other liver inflammatory diseases. PMID: 19101114.

Best regards, and happy holidays to all,

Dave

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