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An itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin
Itch-sensing neurons in your skin are intertwined with your immune cells. Counterintuitively, the molecule that connects them triggers responses that both…
Itching can be uncomfortable, but it’s a normal part of your skin’s immune response to external threats. When you’re itching from an encounter with poison ivy or mosquitoes, consider that your urge to scratch may have evolved to get you to swat away disease-carrying pests.
However, for many people who suffer from chronic skin diseases like eczema, the sensation of itch can fuel a vicious cycle of scratching that interrupts sleep, reduces productivity and prevents them from enjoying daily life. This cycle is caused by sensory neurons and skin immune cells working together to promote itching and skin inflammation.
But, paradoxically, some of the mechanisms behind this feedback loop also stop inflammation from getting worse. In our newly published research, my team of immunologists and neuroscientists and I discovered that a specific type of itch-sensing neuron can push back on the itch-scratch-inflammation cycle in the presence of a small protein. This protein, called interleukin-31, or IL-31, is typically involved in triggering itching.
This negative feedback loop – like the vicious cycle – is only possible because the itch-sensing nerve endings in your skin are closely intertwined with the millions of cells that make up your skin’s immune system.
An itchy molecule
The protein IL-31 is key to the connection between the nervous and immune systems. This molecule is produced by some immune cells, and like other members of this molecule family, it specializes in helping immune cells communicate with each other.
IL-31 is rarely present in the skin or blood of people who don’t have a history of eczema, allergies, asthma or related conditions. But those with conditions like eczema that cause chronic itch have significantly increased skin production of IL-31. There is strong evidence that IL-31 is one of a small set of proteins that immune cells produce that can bind directly to sensory neurons and trigger itching. Small amounts of purified IL-31 injected directly into skin or spinal fluid leads to impressively rapid-onset itching and scratching.
However, when my colleagues and I induced rashes in mice by exposing them to dust mites, we found that itch-sensing neurons turned down the dial on inflammation at the site of itching instead of promoting it. They did so by secreting small molecules called neuropeptides that, in this context, directed immune cells to respond less enthusiastically. In sum, we had discovered an inverse relationship between itching and skin inflammation, tethered by a single molecule.
But if IL-31 triggers itching, which can worsen inflammation by making patients scratch their skin, how does it reduce inflammation?
We found the answer to this paradox in a little-known function of sensory neurons called neurogenic inflammation. This nerve reflex triggers sensory neurons to release various signaling molecules directly into tissues, including specific neuropeptides that promote signs of inflammation like increased blood flow to the skin. Neurogenic inflammation acts within the same nerves that transmit sensory information like itch, pain, touch and temperature, but differs by the path it takes: away from the brain rather than toward it.
We discovered that IL-31 can induce neurogenic inflammation, mapping a direct pathway going from IL-31 through sensory neurons to repress immune cells in the skin. When we engineered mice to be unresponsive to IL-31, we similarly found that they had more activated skin immune cells that produced more inflammation. This means the net effect of IL-31 is to blunt overall inflammation.
IL-31 as potential treatment
Our study shows that IL-31 causes sensory neurons in the skin to perform two very different functions: They signal inward to the spinal cord and brain to stimulate an itching sensation that typically leads to more inflammation, but they also signal back out to the skin and quell inflammation by inhibiting certain immune cells.
Although paradoxical, this makes evolutionary sense. Scratching an itch can feel very satisfying but doesn’t have much utility in the modern world where we’re more likely to suffer from compulsive scratching than encounter stinging nettles. In contrast, unchecked inflammation underlies many chronic autoimmune diseases. Therefore, turning off an immune response in inflamed tissue can be as important as turning it on.
Our discoveries raise important questions about the implications of modifying IL-31 to treat different diseases. For one, it isn’t clear how IL-31-sensing neurons interface with other neuronal circuits that also regulate skin inflammation. Furthermore, some patients have higher levels of allergic proteins in their blood or develop asthma flares when taking existing drugs that target IL-31. IL-31 is also found in some lung and gut cells – how and why would an itch-inducing molecule be present in internal organs?
Anatomical niches where sensory neurons and immune cells converge are present throughout the human body. If an itchy molecule like IL-31 can use neuronal circuitry to dampen an immune response in the skin, similar molecules like those used in migraine drugs could be repurposed to treat skin conditions, too.
Marlys Fassett receives funding from the National Institutes of Health/National Institute of Arthritis, Musculoskeletal and Skin Diseases. She also serves as a grant reviewer for the National Eczema Association.
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Q4 Update: Delinquencies, Foreclosures and REO
Today, in the Calculated Risk Real Estate Newsletter: Q4 Update: Delinquencies, Foreclosures and REO
A brief excerpt: I’ve argued repeatedly that we would NOT see a surge in foreclosures that would significantly impact house prices (as happened followi…
A brief excerpt:
I’ve argued repeatedly that we would NOT see a surge in foreclosures that would significantly impact house prices (as happened following the housing bubble). The two key reasons are mortgage lending has been solid, and most homeowners have substantial equity in their homes..There is much more in the article. You can subscribe at https://calculatedrisk.substack.com/ mortgage rates real estate mortgages pandemic interest rates
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And on mortgage rates, here is some data from the FHFA’s National Mortgage Database showing the distribution of interest rates on closed-end, fixed-rate 1-4 family mortgages outstanding at the end of each quarter since Q1 2013 through Q3 2023 (Q4 2023 data will be released in a two weeks).
This shows the surge in the percent of loans under 3%, and also under 4%, starting in early 2020 as mortgage rates declined sharply during the pandemic. Currently 22.6% of loans are under 3%, 59.4% are under 4%, and 78.7% are under 5%.
With substantial equity, and low mortgage rates (mostly at a fixed rates), few homeowners will have financial difficulties.
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‘Bougie Broke’ – The Financial Reality Behind The Facade
‘Bougie Broke’ – The Financial Reality Behind The Facade
Authored by Michael Lebowitz via RealInvestmentAdvice.com,
Social media users claiming…
Authored by Michael Lebowitz via RealInvestmentAdvice.com,
Social media users claiming to be Bougie Broke share pictures of their fancy cars, high-fashion clothing, and selfies in exotic locations and expensive restaurants. Yet they complain about living paycheck to paycheck and lacking the means to support their lifestyle.
Bougie broke is like “keeping up with the Joneses,” spending beyond one’s means to impress others.
Bougie Broke gives us a glimpse into the financial condition of a growing number of consumers. Since personal consumption represents about two-thirds of economic activity, it’s worth diving into the Bougie Broke fad to appreciate if a large subset of the population can continue to consume at current rates.
The Wealth Divide Disclaimer
Forecasting personal consumption is always tricky, but it has become even more challenging in the post-pandemic era. To appreciate why we share a joke told by Mike Green.
Bill Gates and I walk into the bar…
Bartender: “Wow… a couple of billionaires on average!”
Bill Gates, Jeff Bezos, Elon Musk, Mark Zuckerberg, and other billionaires make us all much richer, on average. Unfortunately, we can’t use the average to pay our bills.
According to Wikipedia, Bill Gates is one of 756 billionaires living in the United States. Many of these billionaires became much wealthier due to the pandemic as their investment fortunes proliferated.
To appreciate the wealth divide, consider the graph below courtesy of Statista. 1% of the U.S. population holds 30% of the wealth. The wealthiest 10% of households have two-thirds of the wealth. The bottom half of the population accounts for less than 3% of the wealth.
The uber-wealthy grossly distorts consumption and savings data. And, with the sharp increase in their wealth over the past few years, the consumption and savings data are more distorted.
Furthermore, and critical to appreciate, the spending by the wealthy doesn’t fluctuate with the economy. Therefore, the spending of the lower wealth classes drives marginal changes in consumption. As such, the condition of the not-so-wealthy is most important for forecasting changes in consumption.
Revenge Spending
Deciphering personal data has also become more difficult because our spending habits have changed due to the pandemic.
A great example is revenge spending. Per the New York Times:
Ola Majekodunmi, the founder of All Things Money, a finance site for young adults, explained revenge spending as expenditures meant to make up for “lost time” after an event like the pandemic.
So, between the growing wealth divide and irregular spending habits, let’s quantify personal savings, debt usage, and real wages to appreciate better if Bougie Broke is a mass movement or a silly meme.
The Means To Consume
Savings, debt, and wages are the three primary sources that give consumers the ability to consume.
Savings
The graph below shows the rollercoaster on which personal savings have been since the pandemic. The savings rate is hovering at the lowest rate since those seen before the 2008 recession. The total amount of personal savings is back to 2017 levels. But, on an inflation-adjusted basis, it’s at 10-year lows. On average, most consumers are drawing down their savings or less. Given that wages are increasing and unemployment is historically low, they must be consuming more.
Now, strip out the savings of the uber-wealthy, and it’s probable that the amount of personal savings for much of the population is negligible. A survey by Payroll.org estimates that 78% of Americans live paycheck to paycheck.
More on Insufficient Savings
The Fed’s latest, albeit old, Report on the Economic Well-Being of U.S. Households from June 2023 claims that over a third of households do not have enough savings to cover an unexpected $400 expense. We venture to guess that number has grown since then. To wit, the number of households with essentially no savings rose 5% from their prior report a year earlier.
Relatively small, unexpected expenses, such as a car repair or a modest medical bill, can be a hardship for many families. When faced with a hypothetical expense of $400, 63 percent of all adults in 2022 said they would have covered it exclusively using cash, savings, or a credit card paid off at the next statement (referred to, altogether, as “cash or its equivalent”). The remainder said they would have paid by borrowing or selling something or said they would not have been able to cover the expense.
Debt
After periods where consumers drained their existing savings and/or devoted less of their paychecks to savings, they either slowed their consumption patterns or borrowed to keep them up. Currently, it seems like many are choosing the latter option. Consumer borrowing is accelerating at a quicker pace than it was before the pandemic.
The first graph below shows outstanding credit card debt fell during the pandemic as the economy cratered. However, after multiple stimulus checks and broad-based economic recovery, consumer confidence rose, and with it, credit card balances surged.
The current trend is steeper than the pre-pandemic trend. Some may be a catch-up, but the current rate is unsustainable. Consequently, borrowing will likely slow down to its pre-pandemic trend or even below it as consumers deal with higher credit card balances and 20+% interest rates on the debt.
The second graph shows that since 2022, credit card balances have grown faster than our incomes. Like the first graph, the credit usage versus income trend is unsustainable, especially with current interest rates.
With many consumers maxing out their credit cards, is it any wonder buy-now-pay-later loans (BNPL) are increasing rapidly?
Insider Intelligence believes that 79 million Americans, or a quarter of those over 18 years old, use BNPL. Lending Tree claims that “nearly 1 in 3 consumers (31%) say they’re at least considering using a buy now, pay later (BNPL) loan this month.”More telling, according to their survey, only 52% of those asked are confident they can pay off their BNPL loan without missing a payment!
Wage Growth
Wages have been growing above trend since the pandemic. Since 2022, the average annual growth in compensation has been 6.28%. Higher incomes support more consumption, but higher prices reduce the amount of goods or services one can buy. Over the same period, real compensation has grown by less than half a percent annually. The average real compensation growth was 2.30% during the three years before the pandemic.
In other words, compensation is just keeping up with inflation instead of outpacing it and providing consumers with the ability to consume, save, or pay down debt.
It’s All About Employment
The unemployment rate is 3.9%, up slightly from recent lows but still among the lowest rates in the last seventy-five years.
The uptick in credit card usage, decline in savings, and the savings rate argue that consumers are slowly running out of room to keep consuming at their current pace.
However, the most significant means by which we consume is income. If the unemployment rate stays low, consumption may moderate. But, if the recent uptick in unemployment continues, a recession is extremely likely, as we have seen every time it turned higher.
It’s not just those losing jobs that consume less. Of greater impact is a loss of confidence by those employed when they see friends or neighbors being laid off.
Accordingly, the labor market is probably the most important leading indicator of consumption and of the ability of the Bougie Broke to continue to be Bougie instead of flat-out broke!
Summary
There are always consumers living above their means. This is often harmless until their means decline or disappear. The Bougie Broke meme and the ability social media gives consumers to flaunt their “wealth” is a new medium for an age-old message.
Diving into the data, it argues that consumption will likely slow in the coming months. Such would allow some consumers to save and whittle down their debt. That situation would be healthy and unlikely to cause a recession.
The potential for the unemployment rate to continue higher is of much greater concern. The combination of a higher unemployment rate and strapped consumers could accentuate a recession.
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The most potent labor market indicator of all is still strongly positive
– by New Deal democratOn Monday I examined some series from last Friday’s Household survey in the jobs report, highlighting that they more frequently…
- by New Deal democrat
On Monday I examined some series from last Friday’s Household survey in the jobs report, highlighting that they more frequently than not indicated a recession was near or underway. But I concluded by noting that this survey has historically been noisy, and I thought it would be resolved away this time. Specifically, there was strong contrary data from the Establishment survey, backed up by yesterday’s inflation report, to the contrary. Today I’ll examine that, looking at two other series.
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