Nav: Home

Lipid that aids normal skin turnover may help psoriasis

November 27, 2018

AUGUSTA, Ga. (Nov. 28, 2018) - A lipid that helps keep skin cell turnover on track may help restore healthy turnover in psoriasis, investigators say.

Topical application of the lipid phosphatidylglycerol, or PG, on a mouse model of psoriasis reduced inflammation as well as characteristic, raised skin lesions, they report in the Journal of Investigative Dermatology.

They had already shown that PG has a role in both regulating the function of the major cell type in our skin called keratinocytes and suppressing skin inflammation.

Now they have the first evidence that PG inhibits toll-like receptor activation by the antimicrobial peptides produced by those skin cells, says Dr. Wendy B. Bollag, cell physiologist in the Department of Physiology at the Medical College of Georgia at Augusta University.

Toll-like receptors are a family of receptors that detect external invaders as well as internal damage signals then activate an immune response. Our skin is our largest organ and front line of defense, and a variety of skin cell types make antimicrobial peptides, which function like an endogenous antibiotic to help the skin protect us.

The common skin condition psoriasis upsets the works by increasing both the production of skin cells and production of these antimicrobials by those cells.

In some patients it may be a problematic immune system that initiates the vicious cycle of skin cells producing proteins called cytokines that call in more immune cells that make more cytokines that cause skin cells to make even more cytokines and excessively proliferate, says Bollag. In others, the antimicrobials may initiate the vicious cycle.

Either way, more antimicrobials get produced which is probably beneficial since psoriasis also impairs the skin's ability to prevent invaders.

But these high levels of antimicrobials also produce an inflammatory response much like an invader's might, resulting in the red, flaky patches that typically surface on high-touch areas like the elbows, forearms and knees and also show up on the scalp and elsewhere, says Bollag, the study's corresponding author.

Because at higher levels, the body sees these protective antimicrobial peptides as danger-associated molecular patterns, or DAMPS, which, as the name indicates, it views as signs of danger. DAMPS then activate toll-like receptors.

It's the increased and chronic level in psoriasis that heightens the awareness and response, says first author Dr. Vivek Choudhary, molecular biologist and physiologist in the MCG Department of Physiology.

Once toll-like receptors get activated, the immune system makes proinflammatory cytokines that bring in T cells, which help drive the immune system attacks.

"It's actually T cells that help maintain the disease," Bollag says, "But we are thinking that the innate immune system is sort of what initiates it," she says of that toll-like receptor activation.

In the continuing vicious cycle, all the immune action prompts the skin cells to actually make more antimicrobials in response to the perceived danger. "It's a natural system that has kind of gone haywire," she says.

The investigators used S100A9 as their representative antimicrobial. In psoriasis, the levels of S100A9 correlate with the severity of the disease and, when treatment works, blood levels of S100A9 decrease.

They found that both in keratinocytes as well as inflammation-promoting immune cells called macrophages, PG suppressed activation of toll-like receptors by DAMPS, in this case S100A9.

Next steps include finding a version of PG that can more easily permeate the skin since the larger lipid is a bit too big to easily pass through the natural barrier. Interestingly, psoriasis hinders the barrier function so PG can initially get through, but when the condition improves, PG's access deteriorates, the investigators note.

They suspect PG's inhibition of toll-like receptors doesn't just happen in psoriasis, but that constant fine tuning of the immune response is among its usual functions.

"You want to be able to dial it up, but not go overboard," Bollag says. "We think that may be part of the job of PG, to basically keep the immune system from going from zero to 60 in one second flat."

This is particularly important in body areas regularly exposed to the elements like the skin, lungs and gastrointestinal tract, she says. Maybe part of the problem with psoriasis is that this fine control no longer works well, she says.

Inflammation in the absence of an infection is a hallmark of psoriasis. The resulting inflammation produces a "feed forward" response: Keratinocytes start to excessively proliferate and abnormally differentiate and the skin thickens.

PG enables the normal differentiation of new skin cells as cells make their way up multiple layers, reach the surface and old cells slough off.

PG is made from glycerin, a natural alcohol, water attractor and key component of many lipids, which helps skin look better and aids this healthy production and maturation of high-turnover skin cells. Glycerin is transported by aquaporin-3, which the MCG investigators believe is decreased in psoriasis versus healthy skin.

Today there are a variety of topical treatments for psoriasis, including vitamin D analogues and glucocorticoids, but nothing that works great for all patients, Bollag says. Part of the problem likely is that psoriasis causes vary and the reality that they are mostly not understood. Systemic drugs also are given that generally suppress the immune response, which have obvious side effects like leaving patients susceptible to infection and cancer.

Bollag doesn't think PG will be a magic bullet either, but may one day be a good option for patients with mild disease or as an adjunct to other therapies.

PG is also a component of surfactant, which enables the airs sacs in the lungs to properly inflate so we can breathe. It's been shown to inhibit inflammation in the lungs induced by microorganisms and that it works there as well through toll-like receptors. Bollag notes these new findings about what happens in the skin are likely applicable to similar conditions, where this so-called "sterile inflammation" occurs in response to substances naturally found in the body.
-end-
Research support includes funding from the National Institutes of Health and a U.S. Department of Veterans Affairs Research Career Scientist Award. MCG medical students Hiral Patel, Elyssa Cohen and Wendi Bao are study coauthors.

Click to see the full study, https://www.jidonline.org/article/S0022-202X(18)32774-X/fulltext.

Medical College of Georgia at Augusta University

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.