Update on retinoic acid, PSC, and IBD

[Guest guest]

The 2007 BASL - Dame Shelia Sherlock Research Medal has recently been

awarded to Dr. Bertus Eksteen, Liver Unit - Queen Hospital,

University Hospitals Birmingham NHS Foundation Trust, for his work on:

" Entero-hepatic lymphocyte homing in the pathogenesis of Primary

Sclerosing Cholangitis (PSC.) "

http://www.basl.org.uk/awards.htm

In Dr. Eksteen's abstract available on the above web page, he talks

about lymphocyte homing to the gut, and how these lymophocytes can be

mis-directed to the liver, potentially causing PSC. He notes the

importance of retinoic acid in inducing the " gut-homing "

characteristics. (I've mentioned the retinoic acid [derived from

vitamin A] connection a few times in the last month or so.)

A recent paper my JR Mora (who has collaborated with Eksteen and

) also hints at the role of retinoids in gut-homing of

regulatory T cells in IBD:

Inflamm Bowel Dis. 2007 Oct 9 [Epub ahead of print]

Homing imprinting and immunomodulation in the gut: role of dendritic

cells and retinoids.

Mora JR

Gastrointestinal Unit, Massachusetts General Hospital, Harvard

Medical School, Boston, Massachusetts.

Lymphocyte migration is at the heart of chronic inflammatory

ailments, including inflammatory bowel disease (IBD). Whereas naïve

lymphocytes migrate to all secondary lymphoid organs, they are mostly

excluded from nonlymphoid peripheral tissues. Upon activation,

lymphocytes change their pattern of adhesion receptors and acquire

the capacity to migrate to extralymphoid tissues. Antigen-experienced

T cells are subdivided into different subsets based on their

expression of homing receptors that favor their accumulation in

specific tissues, such as the skin and the gut mucosa. B cells and

antibody-secreting cells (ASC) also show tissue-tropism, which is

somewhat correlated with the class of immunoglobulin that they

produce. In fact, IgA-ASC are located in mucosal tissues, where they

produce IgA, the main class of antibodies found in secretions.

Although IgA-ASC are usually considered as a homogeneous pool of

cells, those located in the small bowel have some unique migratory

characteristics, suggesting that they are generated under different

conditions as compared to IgA-ASC in other mucosal compartments. Foxp3

(+) regulatory T cells (T(REG)) can also exhibit tissue-specific

migratory potential and recent evidence suggests that T(REG) can be

imprinted with gut-specific homing. Moreover, foxp3(+) T(REG) are

enriched in the small bowel lamina propria, where they can be

generated locally. The present review addresses our current

understanding of how tissue-specific homing is acquired and modulated

on T cells, B cells, and ASC, with a special emphasis on the

intestinal mucosa. Harnessing these mechanisms could offer novel,

effective, and more specific therapeutic strategies in IBD. PMID:

17924560.

I'm assuming that the statement that " ... recent evidence suggests

that T(REG) can be imprinted with gut-specific homing " , is referring

to the role of retinoic acid in this process:

Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y.

Small intestine lamina propria dendritic cells promote de novo

generation of Foxp3 T reg cells via retinoic acid. J Exp Med. 2007

Aug 6;204(8):1775-85.

Dave

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