| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan
2 Department of Tropical Medicine and Parasitology, Keio University School of Medicne, Shinjuku-ku, Tokyo, Japan
3 Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan
4 Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: mamoru.gast{at}tmd.ac.jp.
We have previously demonstrated that mucosal CD4+ T cells expressing high levels of
IL-7 receptor (IL-7Rhigh) are pathogenic cells responsible for chronic colitis. Here we
investigate whether IL-7 is directly involved in the expansion of IL-7Rhigh memory
CD4+ mucosal T cells and the exacerbation of colitis. We first showed that CD4+ lamina
propria lymphocytes (LPLs) from wild-type, TCR
-/-, and recombinase-activating gene
(RAG)-2-/--transferred mice with or without colitis and showed phenotypes of memory
cells, but only CD4+ LPL cells from colitic mice showed IL-7Rhigh. In vitro stimulation
by IL-7, but not IL-15 and thymic stromal lymphopoietin (TSLP), enhanced significant
proliferative responses and survival of colitic CD4+, but not normal CD4+ LPLs.
Importantly, in vivo administration of IL-7 mice accelerated the expansion of IL-7Rhigh
memory CD4+ LPLs and thereby exacerbated chronic colitis in RAG-2-/- mice
transferred with CD4+ LPLs from colitic TCR-/- mice. Conversely, the administration of
anti-IL-7R mAb significantly inhibited the development of TCR-/- colitis with decreased
expansion of CD4+ LPLs. Collectively, the present data indicate that IL-7 is essential for
the expansion of pathogenic memory CD4+ T cells under pathological conditions.
Therefore, therapeutic approaches targeting the IL-7R pathway may be feasible in the
treatment of human inflammatory bowel disease.
This article has been cited by other articles:
|
|
 |
|
  R. Shaykhiev and R. Bals Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis J. Leukoc. Biol., July 1, 2007; 82(1): 1 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. de Latour, H. C. Dujardin, F. Mishellany, O. Burlen-Defranoux, J. Zuber, R. Marques, J. Di Santo, A. Cumano, P. Vieira, and A. Bandeira Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7 Blood, October 1, 2006; 108(7): 2300 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Liu, A. L. Putnam, Z. Xu-yu, G. L. Szot, M. R. Lee, S. Zhu, P. A. Gottlieb, P. Kapranov, T. R. Gingeras, B. F. de St. Groth, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells J. Exp. Med., July 10, 2006; 203(7): 1701 - 1711. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
