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 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.

Expression of HLA-DR antigens in inflammatory bowel disease mucosa: Role of intestinal lamina propria mononuclear cell-derived interferon ?

1988 ◽  
Vol 33 (12) ◽  
pp. 1528-1536 ◽  
Author(s):  
Qin Ouyang ◽  
Mounif El-Youssef ◽  
Belinda Yen-Lieberman ◽  
Wanda Sapatnekar ◽  
Kenneth R. Youngman ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Lamina Propria ◽  
Mononuclear Cell ◽  
Bowel Disease ◽  
Intestinal Lamina Propria ◽  
Hla Dr ◽  
Inflammatory Bowel ◽  
Lamina Propria Mononuclear Cell

Regulatory role of natural killer (NK) cells on antibody responses toBrucella abortus

2010 ◽  
Vol 17 (2) ◽  
pp. 152-163 ◽  
Author(s):  
Ning Gao ◽  
Paula Jennings ◽  
Yuhong Guo ◽  
Dorothy Yuan
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Antibody Responses ◽  
Regulatory Role

Crossover Subsets of CD4+ T Lymphocytes in the Intestinal Lamina Propria of Patients with Crohn’s Disease and Ulcerative Colitis

2017 ◽  
Vol 62 (9) ◽  
pp. 2357-2368 ◽  
Author(s):  
Ji Li ◽  
Aito Ueno ◽  
Marietta Iacucci ◽  
Miriam Fort Gasia ◽  
Humberto B. Jijon ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
T Lymphocytes ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Intestinal Lamina Propria

A key regulatory role of TGFβ in Ulcerative Colitis associated Colon Cancer development

2015 ◽  
Vol 41 (08) ◽  
Author(s):  
MC Fantini ◽  
C Becker ◽  
R Kiesslich ◽  
C Schramm ◽  
M Blessing ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Colon Cancer ◽  
Cancer Development ◽  
Regulatory Role

Unraveling the regulatory role of NK cells on T-cell effector functions: Implications for CNS autoimmunity

2014 ◽  
Vol 275 (1-2) ◽  
pp. 54-55
Author(s):  
Eric Armentani ◽  
Alice Laroni ◽  
Federico Ivaldi ◽  
Roopali Gandhi ◽  
Ilaria Gandoglia ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Regulatory Role ◽  
Effector Functions ◽  
Cns Autoimmunity ◽  
Cell Effector

The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis

2018 ◽  
Vol 214 (8) ◽  
pp. 1149-1155 ◽  
Author(s):  
Milad Sabzevary-Ghahfarokhi ◽  
Mojtaba Shohan ◽  
Hedayatollah Shirzad ◽  
Ghorbanali Rahimian ◽  
Amin Soltani ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Regulatory Role

scholarly journals OP39 Treatment of ulcerative colitis With AMT-101, a novel oral interleukin-10 immunomodulatory fusion biologic that traffics across the intestinal epithelium

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S039-S040
Author(s):  
R Mrsny ◽  
B Kanwar ◽  
T Mahmood
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Lamina Propria ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Oral Gavage ◽  
Intestinal Lamina Propria ◽  
Cynomolgus Monkeys ◽  
Pro Inflammatory Cytokines

Abstract Background While different chronic inflammatory diseases can be correlated with distinct pro-inflammatory cytokines, interleukin-10 (IL-10) represents a central anti-inflammatory cytokine capable of modulating many pro-inflammatory signals. Previous clinical efforts to capture the benefit of IL-10 in suppressing the pro-inflammatory state in inflammatory bowel disease (IBD) patients have been limited by dose-limiting systemic side effects. Methods We have designed a chimaera of human IL-10 genetically fused to a non-toxic and poorly immunogenic fragment of the cholix exotoxin, termed AMT-101, that demonstrated rapid receptor-mediated transcytosis in vitro and in vivo and could activate phospho-STAT3 in cells within the lamina propria following luminal administration (data not shown). Mice with oxazolone-induced colitis were dosed by oral gavage with AMT-101 daily for 12 days, at which time colon tissue and serum were examined for hallmarks of inflammation. Enteric-coated capsules were used to deliver either 1 or 5 mg of AMT-101 to the distal ileum of cynomolgus monkeys; serum was collected to examine PK and PD outcomes in this non-inflamed model. Results Histological changes of colonic tissue associated with oxazolone-induced colitis was blocked by the oral gavage of AMT-101. Increases in serum levels of pro-inflammatory cytokines IL-1b, IL-6, and IL-17A were blunted by AMT-101 treatment. Remarkably, endogenous IL-10 increased in this model in an attempt to correct inflammation, but this was also decreased by the delivery of AMT-101. Cynomolgus monkeys dosed orally with AMT-101 capsules showed very low serum levels compared with those observed after IV injection of 0.5 mg/kg AMT-101. Strikingly, serum levels of IL-1 receptor antagonist (IL-1RA) as an anti-inflammatory PD marker were increased to a greater extent following oral capsule dosing compared with IV administration. Conclusion These studies provide strong pre-clinical evidence that AMT-101 can effectively reach the intestinal lamina propria to delivery biologically-active IL-10 following transcytosis across the intestinal epithelium. Importantly, the gut-selective nature of the responses observed suggests AMT-101 may alleviate the previous issues of dose-limiting side effects observed with systemic administration of IL-10 and point to the intestinal lamina propria as a critical site of IL-10’s immunomodulatory actions. AMT-101 has advanced to the clinic and is currently being evaluated in a Phase1b trial in patients with active ulcerative colitis.

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