scholarly journals Interleukin (IL)-23 mediates Toxoplasma gondii–induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

2009 ◽  
Vol 206 (13) ◽  
pp. 3047-3059 ◽  
Author(s):  
Melba Muñoz ◽  
Markus M. Heimesaat ◽  
Kerstin Danker ◽  
Daniela Struck ◽  
Uwe Lohmann ◽  
...  
Keyword(s):  
T Cells ◽  
Toxoplasma Gondii ◽  
Lamina Propria ◽  
Th17 Cells ◽  
Intestinal Inflammation ◽  
Gelatinase A ◽  
Intestinal Lamina Propria ◽  
Small Intestinal ◽  
Th1 Cytokines

Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23–mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii–induced immunopathology. Moreover, IL-23–dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down-regulated and dispensable. CD4+ T cells were the main source of IL-22 in the small intestinal lamina propria. Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation.

scholarly journals Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis

Oncotarget ◽  
2017 ◽  
Vol 8 (58) ◽  
pp. 98945-98952 ◽  
Author(s):  
Fan Wang ◽  
Pai-Lan Peng ◽  
Xue Lin ◽  
Ying Chang ◽  
Jing Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Nk Cells ◽  
Lamina Propria ◽  
Regulatory Role ◽  
Intestinal Lamina Propria ◽  
Th1 Cytokines

scholarly journals Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism

2013 ◽  
Vol 210 (10) ◽  
pp. 2011-2024 ◽  
Author(s):  
Nathan E. Welty ◽  
Christopher Staley ◽  
Nico Ghilardi ◽  
Michael J. Sadowsky ◽  
Botond Z. Igyártó ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Lamina Propria ◽  
Th17 Cells ◽  
Intestinal Infection ◽  
T Cell Homeostasis ◽  
Cd11b Expression ◽  
Cell Homeostasis ◽  
Intestinal Lamina Propria

Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103+ subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103+CD11b+ LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC–T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-Aβfl/fl mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103+CD11b+ DCs. huLangerin-DTA x BatF3−/− mice lacked both CD103+ LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103+ LP DC subsets control T cell homeostasis through both nonredundant and overlapping mechanisms.

Fas is not essential for lamina propria T lymphocyte homeostasis

2003 ◽  
Vol 285 (2) ◽  
pp. G382-G388 ◽  
Author(s):  
David L. Boone ◽  
Themistocles Dassopoulos ◽  
Sophia Chai ◽  
Marcia Chien ◽  
James Lodolce ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lamina Propria ◽  
T Lymphocyte ◽  
Intestinal Inflammation ◽  
Wild Type ◽  
T Cell Homeostasis ◽  
Brdu Labeling ◽  
Lymphocyte Homeostasis

IL-2 receptor α-deficient (IL2Rα-/-) mice spontaneously accumulate vast numbers of intestinal lamina propria (LP) T cells and develop bowel inflammation. The accumulation of T cells in IL2Rα-/- mice is thought to result, in part, from defective Fas-induced cell death. To understand the role of cell proliferation and death in regulating LP T cells in IL2Rα-/- mice, we have directly examined the proliferation and Fas sensitivity of wild-type, lpr/lpr, and IL2Rα-/- LP T cells. In wild-type mice, 5′-bromodeoxyuridine (BrdU) labeling and Fas susceptibility are greatest in CD44Hi LP T cells. Fas-deficient lpr/lpr mice have normal total numbers of LP T cells, despite an increased proportion of BrdU+ T cells. By contrast, IL2Rα-/- mice possess increased total numbers of LP T cells, despite normal proportions of BrdU+ LP T cells. Finally, wild-type and IL2Rα-/- LP T cells are equivalently Fas sensitive. These results demonstrate that LP T cells proliferate and are Fas-sensitive cells. IL2Rα-/- mice accumulate a large number of these Fas-sensitive LP T cells and clearly differ from Fas-deficient lpr/lpr mice in this regard. Thus our studies reveal that Fas is dispensable for LP T cell homeostasis and suggest that the intestinal inflammation observed in IL2Rα-/- mice is independent of defective Fas-induced cell death.

scholarly journals Intestinal Lamina Propria Retaining CD4+CD25+ Regulatory T Cells Is A Suppressive Site of Intestinal Inflammation

2007 ◽  
Vol 178 (8) ◽  
pp. 4937-4946 ◽  
Author(s):  
Shin Makita ◽  
Takanori Kanai ◽  
Yasuhiro Nemoto ◽  
Teruji Totsuka ◽  
Ryuichi Okamoto ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lamina Propria ◽  
Intestinal Inflammation ◽  
Intestinal Lamina Propria

scholarly journals CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype

2008 ◽  
Vol 20 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Z. Guo ◽  
M. H. Jang ◽  
K. Otani ◽  
Z. Bai ◽  
E. Umemoto ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lamina Propria ◽  
Effector Memory ◽  
Intestinal Lamina Propria ◽  
Memory Phenotype ◽  
Small Intestinal

scholarly journals Ontogeny of FOXP3+Regulatory T Cells in the Postnatal Human Small Intestinal and Large Intestinal Lamina Propria

2009 ◽  
Vol 12 (6) ◽  
pp. 443-449 ◽  
Author(s):  
Jörn-Hendrik Weitkamp ◽  
Erin Rudzinski ◽  
Tatsuki Koyama ◽  
Hernan Correa ◽  
Pranathi Matta ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lamina Propria ◽  
Intestinal Lamina Propria ◽  
Small Intestinal

Gut-associated lymphoid tissue–primed CD4+ T cells display CCR9-dependent and -independent homing to the small intestine

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3447-3454 ◽  
Author(s):  
Hanna Stenstad ◽  
Anna Ericsson ◽  
Bengt Johansson-Lindbom ◽  
Marcus Svensson ◽  
Jan Marsal ◽  
...  
Keyword(s):  
T Cells ◽  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Cd4 T Cells ◽  
Lymphoid Tissue ◽  
Cd4 T Cell ◽  
Intestinal Lamina Propria ◽  
Mesenteric Lymph ◽  
Receptor Profile ◽  
Small Intestinal

CD4+ T-cell entry to the intestinal mucosa is central to the generation of mucosal immunity as well as chronic intestinal inflammation, yet the mechanisms regulating this process remain poorly defined. Here we show that murine small intestinal CD4+ lamina propria lymphocytes express a heterogeneous but restricted array of chemokine receptors including CCR5, CCR6, CCR9, CXCR3, and CXCR6. CD4+ T-cell receptor transgenic OT-II cells activated in mesenteric lymph nodes acquired a distinct chemokine receptor profile, including expression of CCR6, CCR9, and CXCR3 that was only partially reproduced in vitro after priming with mesenteric lymph node dendritic cells. A subset of these effector CD4+ T cells, expressing CD69 and α4β7, entered the intestinal lamina propria and the majority of these cells expressed CCR9. CCR9–/– OT-II cells were disadvantaged in their ability to localize to the intestinal lamina propria; however, they were readily detected at this site and expressed α4β7, but little CCR2, CCR5, CCR6, CCR8, CCR10, CXCR3, or CXCR6. Thus, whereas CD4+ T cells activated in gut-associated lymphoid tissue express a restricted chemokine receptor profile, including CCR9, targeting both CCR9-dependent and CCR9-independent entry mechanisms is likely to be important to maximally inhibit accumulation of these cells within the small intestinal mucosa.

PL1-2. The role of inflammasome processed cytokines in driving Th17 cells and IL-17 producing γδ T cells in infection and autoimmunity

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 3
Author(s):  
Kingston H.G. Mills ◽  
Aisling Dunne ◽  
Lara Dungan ◽  
Jean Fletcher ◽  
Sarah Higgins ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Γδ T Cells

scholarly journals Intestinal myofibroblasts: targets for stem cell therapy

2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Cell Therapy ◽  
Lamina Propria ◽  
Stem Cell Therapy ◽  
Intestinal Inflammation ◽  
Mesenchymal Cells ◽  
Hematopoietic Stem ◽  
Intestinal Lamina Propria

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

Abstract 3598: Critical Role of Th17-CD4 + T cells in Angiogenic Response to Hindlimb Ischemia in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takeki Hata ◽  
Masafumi Takahashi ◽  
Masanori Kawaguchi ◽  
Yuichiro Kashima ◽  
Yuji Shiba ◽  
...  
Keyword(s):  
T Cells ◽  
Blood Flow ◽  
Th17 Cells ◽  
Critical Role ◽  
Interleukin 17 ◽  
Hindlimb Ischemia ◽  
Capillary Formation ◽  
Angiogenic Response ◽  
Flow Perfusion

Background: Accumulating evidence indicates that CD4 + T cells contribute to the development of collateral vesssels in ischemic tissue; however, little is known about the responsible subset of CD4 + T cells in the induction of angiogenesis. Th17 cells are recently identified as a new subset of CD4 + T cells and have been associated with the pathogenesis of certain autoimmune diseases. Th17 cells specifically secrete interleukin-17 (IL-17) and regulate various biological functions. The purpose of this study is to investigate the role of CD4 + T and Th17 cells in angiogenic response to hindlimb ischemia. Methods and Results: Unilateral hindlimb ischemia was produced in wild-type (WT: C57BL/6, 8- to 10-week-old) mice treated with or without a neutralizing antibody against CD4. Blood flow perfusion and capillary formation were assessed by using a laser Doppler perfusion imaging (LDPI) and CD31 immunostaining, respectively. Well-developed collateral vessels and capillary formation were observed in WT mice in response to hindlimb ischemia. Treatment with a neutralizing anti-CD4 antibody resulted in almost complete CD4 + T cell depletion (flow cytometry analysis, control: 45.4% vs. antibody: 1.0%) and a significant decrease in angiogenesis after the induction of hindlimb ischemia (LDPI, 21 days, control: 0.61 ± 0.1 vs. antibody: 0.41 ± 0.1, p<0.05). IL-17-deficient (IL-17 −/− ) mice also showed a significant reduction of blood flow perfusion, compared with WT mice (LDPI, day 14: 0.56 ± 0.3 vs. 0.31 ± 0.2, p<0.05; day 21: 0.66 ± 0.3 vs. 0.37 ± 0.3, p=0.05). IL-17 −/− mice had severe ischemic damage of the limb and resulted in a 25% incidence of autoamputation by day 21 (no limb loss in WT mice). Furthermore, capillary formation was also decreased significantly in IL-17 −/− mice (692.9 ± 165.6/mm 2 vs. 1223.3 ± 267.3/mm 2 , p<0.01). Conclusion : These findings demonstrate that Th17 cells, a new subset of CD4 + T cells, contribute to the angiogenic response to hindlimb ischemia and provide new insights into the mechanism by which T cells promote collateral development and angiogenesis.

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