Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10, 2019, Rojas et al

[Webdog]

Study:
Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10
https://doi.org/10.1016/j.cell.2018.11.035

Press Release:
Gut Immune Cells Cut Inflammation in Multiple Sclerosis
https://www.ucsf.edu/news/2018/12/412941/gut-immune-cells-cut-inflammation-multiple-sclerosis

Researchers at the University of Toronto and UC San Francisco have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis (MS), and that increasing the number of these cells blocks inflammation entirely in a preclinical model of the disease.

The cells in question are plasma cells — white blood cells that originate as B cells in the bone marrow but change their behavior when triggered by microbes in the gut. Studying mice and samples from human MS patients, the researchers found that plasma cells that reside in the gut and produce Immunoglobulin A (IgA) antibodies appear to migrate to the central nervous system and produce an anti-inflammatory effect during MS flare-ups.

Specifically, the UCSF team found evidence that IgA was decreased in fecal samples from patients with active MS neuroinflammation, suggesting that the inflammation-suppressing cells had been recruited to help fight the patients’ disease.

One promising aspect of the new research is that increasing the number of IgA plasma cells that migrate from the gut to the brain eradicated neuroinflammation in mice. A therapeutic approach might aim to expand the number of these cells in the gut, enabling a plentiful supply that could move to the brain and dampen inflammation.

"Until now, no one has really studied these IgA-producing plasma cells in the context of disease, but we are now examining them in detail in patients with MS to begin to understand how we might manipulate them to help treat neuroinflammatory disease.”

A key next step for the researchers is to figure out what microbes in the gut promote the generation of immunosuppressive IgA plasma cells. “If we can understand what these cells are reacting to, we can potentially treat MS by modulating our gut commensals,” said Gommerman, referring to the bacteria that live in the healthy gut. “That might be easier than getting drugs into the brain, which is a strategy that hasn’t always worked in MS.”

 

[Kalliope]

 

[Jonathan Edwards]

My impression from the paper abstract is that yet again the authors have no understanding of the problem they are trying to solve. Since about 2000 this seems to have become the norm in immunology.

What is perhaps more worrying is that Collins, as head of NIH, does not even seem to understand the abstract, let alone what it might imply. These are worrying times when the people in charge of medical science seem not to understand common sense, let alone the science.

 

[Kalliope]

 

[Jonathan Edwards]

Total confusion!