Do mucosal T cells prevent intestinal inflammation?

2000 ◽  
Vol 118 (5) ◽  
pp. 974-977 ◽  
Author(s):  
Mitchell Kronenberg ◽  
Hilde Cheroutre
Keyword(s):  
T Cells ◽  
Intestinal Inflammation ◽  
Mucosal T Cells

scholarly journals The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease

2002 ◽  
Vol 195 (9) ◽  
pp. 1129-1143 ◽  
Author(s):  
M.F. Neurath ◽  
B. Weigmann ◽  
S. Finotto ◽  
J. Glickman ◽  
E. Nieuwenhuis ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Intestinal Inflammation ◽  
Retroviral Transduction ◽  
Ifn Γ ◽  
Mucosal T Cells ◽  
Chronic Intestinal Inflammation

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-γ/interleukin (IL)-4 and transforming growth factor (TGF)-β activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L+ CD4+ T cells exacerbated colitis in reconstituted SCID mice, T-bet–deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet–deficient CD62L− CD4+ T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-β signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-γ/IL-4 and TGF-β responses and the development of chronic intestinal inflammation in T cell–mediated colitis. Furthermore, TGF-β was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-β and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell–mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.

scholarly journals Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis

2004 ◽  
Vol 200 (11) ◽  
pp. 1511-1517 ◽  
Author(s):  
Bertus Eksteen ◽  
Allister J. Grant ◽  
Alice Miles ◽  
Stuart M. Curbishley ◽  
Patricia F. Lalor ◽  
...  
Keyword(s):  
T Cells ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Cell Adhesion Molecule ◽  
Intestinal Inflammation ◽  
Aberrant Expression ◽  
Inflammatory Bowel ◽  
Mucosal T Cells ◽  
Cell Adhesion Molecule 1 ◽  
Infiltrating Lymphocytes

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150–157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates α4β7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD.

scholarly journals Mucosal T Cells Bearing TCRγδ Play a Protective Role in Intestinal Inflammation

2004 ◽  
Vol 173 (2) ◽  
pp. 1390-1398 ◽  
Author(s):  
Kyoko Inagaki-Ohara ◽  
Takatoshi Chinen ◽  
Goro Matsuzaki ◽  
Atsuo Sasaki ◽  
Yukiko Sakamoto ◽  
...  
Keyword(s):  
T Cells ◽  
Intestinal Inflammation ◽  
Protective Role ◽  
Mucosal T Cells

scholarly journals Cutting Edge: Heligmosomoides polygyrus Induces TLR4 on Murine Mucosal T Cells That Produce TGFβ after Lipopolysaccharide Stimulation

2006 ◽  
Vol 176 (2) ◽  
pp. 726-729 ◽  
Author(s):  
M. Nedim Ince ◽  
David E. Elliott ◽  
Tommy Setiawan ◽  
Arthur Blum ◽  
Ahmed Metwali ◽  
...  
Keyword(s):  
T Cells ◽  
Cutting Edge ◽  
Heligmosomoides Polygyrus ◽  
Mucosal T Cells

scholarly journals Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis

2014 ◽  
Vol 307 (2) ◽  
pp. G177-G186 ◽  
Author(s):  
Yuying Liu ◽  
Dat Q. Tran ◽  
Nicole Y. Fatheree ◽  
J. Marc Rhoads
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Necrotizing Enterocolitis ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RBlo separates T effector/memory (Tem) cells from naive (CD44−CD45RBhi) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4+Foxp3+ regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.

Thymus-Independent Mucosal T Cells Regulate the Increase in Paneth and Intermediate Cells in the Small Intestine of Mice Infected with T. Spiralis

2001 ◽  
Vol 100 (s44) ◽  
pp. 13P-14P
Author(s):  
M Kamal ◽  
D Wakelin ◽  
A Smith ◽  
A Ouellette ◽  
DK Podolsky ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Intermediate Cells ◽  
Mucosal T Cells

scholarly journals RORγt is dispensable for the development of intestinal mucosal T cells

2008 ◽  
Vol 1 (3) ◽  
pp. 198-207 ◽  
Author(s):  
T Naito ◽  
T Shiohara ◽  
T Hibi ◽  
M Suematsu ◽  
H Ishikawa
Keyword(s):  
T Cells ◽  
Mucosal T Cells
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