colitis tagged posts

Researchers Identify why Cancer Immunotherapy can cause Colitis

green background intestines in pink
Jacob Dwyer, Michigan Medicine

Researchers at the University of Michigan Health Rogel Cancer Center have identified a mechanism that causes severe gastrointestinal problems with immune-based cancer treatment.

They also found a way to deliver immunotherapy’s cancer-killing impact without the unwelcome side effect.

The findings are published in Science.

“This is a good example of how understanding a mechanism helps you to develop an alternative therapy that’s more beneficial. Once we identified the mechanism causing the colitis, we could then develop ways to overcome this problem and prevent colitis while preserving the anti-tumor effect,” said senior study author Gabriel Nunez, M.D., Paul de Kruif Professor of Pathology at Michigan Medicine.

Immunotherapy has emerged as a pr...

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Unlocking Secrets of Immune System could help Combat Colitis

An intrinsic complement-NLRP3 axis regulates human TH1 responses. T cell receptor activation and CD46 costimulation trigger NLRP3 expression and intracellular C5a generation. Subsequent intracellular C5aR1 engagement induces ROS production (and possibly IL1B gene transcription) and NLRP3 assembly, which in turn mediates IL-1β maturation. Autocrine IL-1β promotes TH1 induction (IFN-γ production) but restricts TH1 contraction (IL-10 coexpression). C5aR2 cell surface activation by secreted C5a negatively controls these events via undefined mechanisms. Dysfunction of this system contributes to impaired TH1 responses in infection or increased TH17 responses during intestinal inflammation.

An intrinsic complement-NLRP3 axis regulates human TH1 responses. T cell receptor activation and CD46 costimulation trigger NLRP3 expression and intracellular C5a generation. Subsequent intracellular C5aR1 engagement induces ROS production (and possibly IL1B gene transcription) and NLRP3 assembly, which in turn mediates IL-1β maturation. Autocrine IL-1β promotes TH1 induction (IFN-γ production) but restricts TH1 contraction (IL-10 coexpression). C5aR2 cell surface activation by secreted C5a negatively controls these events via undefined mechanisms. Dysfunction of this system contributes to impaired TH1 responses in infection or increased TH17 responses during intestinal inflammation.

Researchers have unlocked secrets of our ancient immune system...

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Starvation Signals control Intestinal Inflammation in mice

Research discoveries by Bali Pulendran (seated) and colleagues point to possible new treatment strategies for inflammatory bowel diseases and autoimmune diseases in humans. Credit: Image courtesy of Emory Health Sciences

Research discoveries by Bali Pulendran (seated) and colleagues point to possible new treatment strategies for inflammatory bowel diseases and autoimmune diseases in humans. Credit: Image courtesy of Emory Health Sciences

Intestinal inflammation in mice can be dampened by subjecting them briefly to a diet restricted in amino acids. The findings, made by Bali Pulendran and colleagues at Emory University, highlight an ancient connection between cellular mechanisms to sense nutrient availability and control of inflammation. They also suggest that a low protein diet – or drugs that mimic its effects on immune cells – could be tools for the treatment of inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis.

This protective effect was shown to be mediated by molecule GCN2, wh...

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