The genetics of inflammatory bowel disease

[Guest guest]

Dear All;

The file just uploaded to the " Files/Research " folder, covers my

favorite topics these days .... genetics, and the role of Th17 cells

in inflammatory bowel disease.

While the article gives good coverage of the involvement of

interleukin-23 in Th17 production, and how the Th17 cells promote

inflammation via synthesis of interleukin-17, it doesn't cover the

effects of retinoic acid (a vitamin A metabolite) in switching off

Th17 cell production and stimulating gut-homing, anti-inflammatory

regulatory T cells (Tregs):

Kang SG, Lim HW, Andrisani OM, Broxmeyer HE, Kim CH. Vitamin A

Metabolites Induce Gut-Homing FoxP3+ Regulatory T Cells.

J Immunol. 2007 Sep 15;179(6):3724-33. PMID: 17785809.

Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic

acid receptor-alpha favours regulatory T cell induction at the

expense of IL-17-secreting T helper cell differentiation. Eur J

Immunol. 2007 Sep;37(9):2396-9. PMID: 17694576.

Mucida D, Park Y, Kim G, Turovskaya O, I, Kronenberg M,

Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation

mediated by retinoic acid. Science. 2007 Jul 13;317(5835):256-60.

PMID: 17569825.

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. PMID: 17620362.

Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. All-trans retinoic

acid mediates enhanced T reg cell growth, differentiation, and gut

homing in the face of high levels of co-stimulation. J Exp Med. 2007

Aug 6;204(8):1765-74.

Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM,

Belkaid Y, Powrie F. A functionally specialized population of mucosal

CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and

retinoic acid-dependent mechanism. J Exp Med. 2007 Aug 6;204(8):1757-

64. PMID: 17620361.

von Boehmer H. Oral tolerance: is it all retinoic acid? J Exp Med.

2007 Aug 6;204(8):1737-9. PMID: 17620364.

Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY.

Retinoic acid imprints gut-homing specificity on T cells. Immunity.

2004 Oct;21(4):527-38. PMID: 15485630.

Mora JR, von Andrian UH. Retinoic acid: an educational " vitamin

elixir " for gut-seeking T cells. Immunity. 2004 Oct;21(4):458-60.

PMID: 15485623.

Johansson-Lindbom B, Agace WW. Vitamin A helps gut T cells find their

way in the dark. Nat Med. 2004 Dec;10(12):1300-1. PMID: 15580252.

I continue to believe that this vitamin A connection will eventually

be very important in understanding IBD (and hopefully PSC also).

Best regards,

Dave

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