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Interleukin 17 producing and responding neutrophils exhibit enhanced microbial killing activity

Ema

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Midwest USA
http://www.eurekalert.org/pub_releases/2014-03/cwru-nis032414.php


PUBLIC RELEASE DATE:
24-Mar-2014



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Contact: Jessica Studeny
Jessica.studeny@case.edu
216-368-4692
Case Western Reserve University
Nature Immunology study finds novel population of neutrophils
Interleukin 17 producing and responding neutrophils exhibit enhanced microbial killing activity
Case Western Reserve University researchers have discovered a novel population of neutrophils, which are the body's infection control workhorses. These cells have an enhanced microbial killing ability and are thereby better able to control infection.

Neutrophils, the body's most abundant type of white blood cells, have long been regarded as first responders that kill fungi, bacteria, and other pathogens. In a study published in the February issue of Nature Immunology, Case Western Reserve researchers explain that they have found the mechanism of action of a newly discovered population of neutrophils. A sub-population of neutrophils produce a cytokine called Interleukin 17 (IL-17) to regulate the body's response to the infection; however the same cells were discovered to have enhanced microbial killing activity.

These cells may behave as a double-edged sword as although they have an enhanced ability to control infection, they also have the potential to cause inflammation that results in tissue damage, and further studies are underway to regulate these activities.

The researchers, from the Department of Ophthalmology and Visual Sciences, showed that neutrophils are the first cells discovered to both produce and respond to IL-17, a messenger protein that stimulates an inflammatory response at the site of infection, and can recruit additional neutrophils to the site of infection. They also found in cornea infections that neutrophils have an important role in killing fungi, but can also break down the corneal structure and result in tissue damage and visual impairment.

"In healthy individuals, this IL-17 feedback action gives these neutrophils an enhanced ability to respond to bacterial and fungal infections," said senior author Eric Pearlman, PhD, professor and director of research for the Department of Ophthalmology and Visual Sciences. "Yet in people with certain immune abnormalities or genetic mutations, this process can produce high levels of chronic inflammation. When an inflammatory response does occur, it can lead to the kind of tissue damage associated with autoimmune diseases like psoriasis, rheumatoid arthritis, multiple sclerosis and lupus."

"Although T cells are a major source of IL-17, the neutrophils arrive at the site of infection first," said first author Patricia Taylor, PhD, a postdoctoral researcher in Pearlman's laboratory. Therefore fungal killing and tissue damage take place even before the T cells arrive.

Pearlman and colleagues conducted their initial research on individuals with fungal keratitis, an inflammatory eye infection, at the Aravind Eye Hospital in Madurai, in south India. The hot, humid climate combined with agriculture results in high levels of airborne spores and a high prevalence of corneal ulcers caused by these fungi.

"We found an abundance of IL-17 being made in the infected corneas, and identified neutrophils as a source of the IL-17 in the cornea," Pearlman said.

"This is just the tip of the iceberg," he added. "There are so many potential diseases these IL-17 producing neutrophils could play a role in. We're already finding other unexpected gene expressions. In the short term, we will work to further characterize these cells, see what other areas are being regulated that impact microbial killing and inflammatory response."



 

SOC

Senior Member
Messages
7,849
Wondering how this might related to the fact that I have 0.000 pg/ml (yes, really) IL-17 in my blood....
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Wondering how this might related to the fact that I have 0.000 pg/ml (yes, really) IL-17 in my blood....
What testing did you have that showed this?

Considering it should come from both T cells and neutrophils, that does seem very odd.
 

SOC

Senior Member
Messages
7,849
What testing did you have that showed this?

Considering it should come from both T cells and neutrophils, that does seem very odd.
My testing was done at Dr Klimas' and Fletcher's immunology lab at University of Miami, so I'm pretty confident that the testing is sound. It's been low as long as we've been testing (about 2 years), but this is the worst (duh, like it can get worse than 0.00). My IL-23, which is related, is down in the 10%ile as well. Consistently very low levels of both of these cytokines has been an ongoing issue for me.

My IL-2 and IL-10 are also came up 0.000, but they've been up and down over time, so there's not a clear pattern.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
My testing was done at Dr Klimas' and Fletcher's immunology lab at University of Miami, so I'm pretty confident that the testing is sound. It's been low as long as we've been testing (about 2 years), but this is the worst (duh, like it can get worse than 0.00). My IL-23, which is related, is down in the 10%ile as well. Consistently very low levels of both of these cytokines has been an ongoing issue for me.

My IL-2 and IL-10 are also came up 0.000, but they've been up and down over time, so there's not a clear pattern.
I didn't mean to imply/infer that the testing wasn't sound. I was just curious because I've never had it done, so I wondered where you got it done!

Do they have reference ranges for the cytokines? I mean, I wonder if it is *normal* to have near 0 level of a cytokine most of the time unless there is a need for it to spike to fight something?
 

SOC

Senior Member
Messages
7,849
quote="Ema, post: 444854, member: 4199"]I didn't mean to imply/infer that the testing wasn't sound. I was just curious because I've never had it done, so I wondered where you got it done!

Do they have reference ranges for the cytokines? I mean, I wonder if it is *normal* to have near 0 level of a cytokine most of the time unless there is a need for it to spike to fight something?[/quote]
:) I don't think it's a standard test. It's their Cytokine Multiplex-18. It tests 18 different cytokines. I always have 6-10 of the 18 out of range either high or low (often very high and very low).

The data is given in percentiles rather than with a reference range. The goal range for all the cytokines is 25th - 75th percentile. 10th-25th percentile is considered low. Below 10th percentile is very low. The goal range indicates the range of normal functioning, so 0.000 pg/ml (below the 10th percentile) is apparently quite unusual.

Some of my out-of-range cytokines switch between high and low, so I imagine that might suggest functional spiking, but my IL-17 and IL-23 have been consistently low or very low. :(
 

wastwater

Senior Member
Messages
1,281
Location
uk
I have a genetic eye condition axenfeld riegers syndrome and possibly IL-17 involvement
 

wastwater

Senior Member
Messages
1,281
Location
uk
A person with fibromyalgia gives birth to a child with axenfeld riegers syndrome is this mecfs turned up to 11 with genetic hit points clearly seen, l wonder or not
 
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