Episode 56: What a parent should know about eczema and a baby’s immune system
Every parent wants to protect their baby — but what if the window to prevent lifelong allergies is smaller than anyone realized? Scientists have discovered that a newborn's immune system doesn't just work differently from an adult's; it's actually wired to overreact in ways that can set the stage for eczema and allergies before you even know it's happening. The culprit? A hormone, missing in babies, that keeps the immune system in check.
In this episode, Dr. Shruti Naik reveals what's really going on beneath your baby's skin, and what it could mean for the future of allergy prevention. If you like our podcast, please consider supporting it with a tax-deductible donation.
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EP56 Immune response in babies
Lynita: Hello, and welcome to the podcast. We often talk about a time in early infancy where the allergic path starts, because babies aren't born allergic. We know that when common allergens enter the skin, they can trigger skin inflammation that could lead to stronger allergic reactions later in life.
However, until now, we have not understood why this time is so important. Now we are learning that in early life, a baby's immune system reacts differently. For parents, this means that protecting your baby's skin right from the start could make a real difference to the rest of their lives.
Joining us to explain the details, is an international leader in immunology and tissue stem cell biology, Associate Professor in Immunology and Dermatology, and the Director of the Tissue Repair Program at Icahn School of Medicine, Mount Sinai: Dr. Shruti Naik.
Welcome to the podcast.
Dr. Naik: Thank you for having me. It's a pleasure to be here.
Lynita: Dr. Naik, your research is really opening our eyes to how this early life window of allergic opportunity works, and it's really a big breakthrough. But it's also really complex. So before we talk about your work, can you please help us understand the immune system?
Dr. Naik: Sure.
Your immune system is essentially a liquid organ. It lives all over your body. Every cell in your body has touched an immune cell, right? It’s surveilling your body at all times, and one of the big jobs it does is it fights off the bad guys, microbes, pathogens, the infections, the viruses.
And so the immune system has developed different strategies to eliminate different types of microbes and how our body copes with damage.
Broadly, there's - three types of immune responses.
There's Type 1, which is dealing with viruses or microbes that live inside of cells. And it kills the infected cell.
There's Type 2, which is really driven by communication molecules that immune cells use to talk to other cells, these are called IL-4, interleukin 4, and IL-13. And the reason this arm of immunity evolved actually was to cope with parasites. Because what this type of immunity allowed the body to do is, for instance, if you have a parasite in your gut, it would promote gut contraction to expel these parasites out.
And then there's type 3 immunity, and this makes factors called IL-17. And it helps kill the microbes that live outside of cells. And it also helps sometimes with wound healing.
So those are the three broad classes of how the immune system responds to deal with infectious pathogens.
Lynita: Okay.
So it's the type two immune system that's responsible for allergic reactions. It's the one that's trying to expel things from our bodies, and that's where the IL-4 and 13 come into play. IL being short for interleukin.
And just to explain the terminology a little further, these interleukins are a type of cytokine that signal immune cells when it's time to act. There are many types of cytokines, and we just number them so we can tell them apart.
And it's these interleukins, specifically 4 and 13 in our type two immune system, that are overreacting in an allergic person. Is that correct?
Dr. Naik: That is correct. So, essentially, to your body, it's almost like a parasitic danger that's there or a wound, and its wires are confused, And sometimes you also see Type 17 responses in allergies, but with Dupixent, the proof is in the pudding. So Dupixent is a therapeutic that directly suppresses Type 2 immunity by blocking the ability of, IL-4, and IL-13 to work. And It's proven to be really successful, and so that really tells us that Type 2 is at the heart of this.
It's a really remarkable therapy because we have learnt how to fuddle with our immune system and say, "No, you're being bad now. Let's stop. Now you're harming me instead of helping me fight off bad guys."
Lynita: Sure. Yeah, it is quite remarkable.
Let's talk a little bit about babies now because babies' immune systems aren't the same as children's or adults even. Can you explain to us: how is a baby's immune system different to a toddler?
Dr. Naik: Yeah, infant, yeah. So this is an area that's actually not very well understood, and for a very good reason, it's very hard to study babies, right? One of the things we have to do as scientists if we wanna understand the immune system is to study it in the blood or in tissues, but I would never, ever ask that of a mother, it's unethical. So, there's very practical reasons why we don't know so much. And this is where animal models are very helpful because then we can actually understand what is happening in the system, and see if some of those rules apply to humans. This is exactly how we discovered IL-4. This is exactly how we discovered IL-13. This is exactly how we discovered type 1-2-3 immunity. works.
So that's what we did. We looked at mice at very young ages, and what we realized is that, the baby's immune system is not absent, it's not weaker, it's not a dampened down version of the adult immune system. The rules by which it's seeing the world are just different. And the reason it's different is because if you think about it, you've been in a womb. You've been growing in that warm, luscious, sterile environment, and then you come out into the world, and it's covered with stuff. And this new baby is just adjusting to a world with food and microbes and dust and pollen and just everything in the air. And it is this moment of transition to the living world. And the immune system is learning and is growing as it adjusts.
What we found in our studies, actually many of these types of immunity are still active and can still function in babies. So it's not that they're not working as we had thought for a very long time. And this is where the eczema risk, the allergy risk comes in, because they're seeing these allergens through a disrupted skin barrier. And the way they react is very different. So in some cases what we found is that in early life, you are almost reacting more than you would as an adult because you're not calibrated. Your system is still calibrating.
Lynita: Sure
Dr. Naik: So essentially we are one of the first studies to start looking at it in this way. And there's a lot more science to be done to understand what are those rules that are different in babies and in young infants.
Lynita: It makes sense when you explain it like that, we've come from this sterile environment. Our bodies have to learn how much to react to something, and the biggest thing being exposed to the environment is our skin as a newborn. And so this is where it all begins, determining how much we will react to the things that we are exposed to. And I guess it explains why we're not born with allergies.
Dr. Naik: This is a really good point because I think, one of the things that scientists are realizing is the way the immune system reacts, for instance, in your skin versus through your intestine, may be very different. And so we really need to know if your immune system is seeing something coming through the skin versus the food that you're eating, how is that different?
And how can we understand the different rules to say, "Let's shut off these bad reactions that are happening in the skin early so we can completely cut off the later in life allergies that come.
Lynita: Wow. Your research is really quite groundbreaking in how it's explaining what's going on in that early window. Do you have an idea of when this window roughly is?
Dr. Naik: We really don't know, because the developmental stages in humans are a little bit different than in mice, right? And so those transition periods, that needs to be studied. I just wanna emphasize that we need moms to advocate for this kind of science.
Lynita: Absolutely. At Global Parents for Eczema Research, we are doing our very best.
Dr. Naik: Thank you, and I'll share with you actually the lead author in my lab who really spearheaded the study. She started it because her son had very severe eczema.
And as a scientist, she went to the scientific literature and she said, “Wait a minute. We actually don't know anything about why babies in early life get eczema. Like, nothing.” So it's a mother's motivation that drew all this science out
Lynita: Wow. Excellent. Global Parents for Eczema Research actually is now funding research and we definitely invite research proposals from scientists that are coming to eczema research from a parent perspective. So visit www.gper.org/grants for more information.
So let's talk about what you found that was unique about a baby's immune system and why they reacted ?
Dr. Naik: Yeah, so this was completely unexpected. When we exposed little newborn pups to allergens on their skin, they reacted really badly. It was like an eczema rash. But when we gave adult mice the same amount of allergen, they didn't react at all. They did react in that they had an immune response, but it wasn't a huge inflammation. So there's something inherently different in the way these two skin immune systems work. And when we started dissecting the immune cells and how they worked in pup skin, we found something remarkable.
One of the key sensor immune cells is called a dendritic cell. This is a cell that hangs out all over your body, and its only job is to survey your tissues and say, "Is something right? Is something wrong?"
So when an allergen comes in, in adult skin, that dendritic cell is gonna pick it up, and it's gonna travel through your lymph, and it's gonna go to your lymph nodes. And your lymph nodes are where all of your T cells and other immune cells hang out. It's like a town square of immune cells, and it's gonna turn on the immune response. And that's the normal way these cells work. But in pups, these immune cells, of course, some of them went to the town centers and did their business and turned on the immune response, but they also started activating locally in the skin, Putting out tons of inflammatory factors right where they were,
Lynita: Right
Dr. Naik: and quickly turning on inflammation in their vicinity. And so that led to a rash, this flare and this was very unique to the pup skin. It did not happen in the adult mice. So it really said that the way the cell reacts depends on the age of the animal. And in early life it's hardwired to hyper react in a certain way.
Lynita: So in our body we have these things called dendritic cells, which are out there detecting anything that might be bad or is neutral.
Dr. Naik: Yeah
Lynita: And in adults, dendritic cells, take that information and they ship it back to the town center, which is where the immune system has its conference and says, "This is bad or good, and we need to do something about it or not." But in babies, the dendritic cells do send it back, but they also go, “We need to do something right now, right where we are before we even go and consult.” And that's the difference between adults and babies. Their reaction is instantaneous and localized.
Dr. Naik: That's exactly right. It's really, this rapid response that's happening right there on the moment and..
Lynita: Yeah
Dr. Naik: triggers that flare, And so one of the things we wanna understand is, does this behavior now stick around, and is this what's allowing for flaring?
We don't know. But if we could understand how these cells are functioning, we could interrupt them, right? We could interrupt the disease when it first starts.
And I think that's the opportunity, spending time to learn how to carefully do that. Because if you don't spend the time on the science, then you're not gonna develop a therapeutic that will be safe and effective.
Lynita: Absolutely.
Dr. Naik: So, second big surprise: your internal hormone system. One of them is called the HPA the hypothalamic pituitary axis. You don't have to remember the name. There won't be a quiz at the end, I promise. But basically this is what controls your healthy levels of cortisol.
We always say cortisol is like a dirty little word, it's a stress hormone. Turns out it's just a normal part of your physiology, and only when things go completely awry does this hormone go up and down. But there's a normal balance.
Lynita: Cortisol is sometimes referred to as a steroid.
Dr. Naik: It is a steroid hormone. That's right. Cortisol is like a trigger word for people 'cause they just associate it with stress, right? But we all have cortisol in our bodies at all times. Even when you're at a yoga retreat, you have cortisol. It's just a normal basal part of your life.
What we realized, in the baby mice was that they don't have the basal level of cortisol. They are just developing their HPA or the thing that makes cortisol. And so in fact, when we compared the pups and the adults, the adults had normal baseline levels, and the pups had zero, zippy, no cortisol. So just their basal levels are still forming. And we also know this in babies the HPA or the - cortisol producing machinery is not set, it's developing. And so this absence of normal basal levels of cortisol actually was the reason why these dendritic cells are behaving this way. And as the normal levels of cortisol were restored, the hyperactivation, that rapid response of the dendritic cells in the skin went away.
Lynita: Right
Dr. Naik: And so it's just the system is hardwired, we think, to have these reactive dendritic cells in babies because they have to come into this new world and cope with threats. And, what if an infection shows up? You need to react quickly, right?
Lynita: Yeah
Dr. Naik: This probably evolved before we had industrialization in the Western world. And so now these dendritic cells they're looking at allergens as threats, um, that we should attack and they're misdirecting the response.
Lynita: Okay. So what I'm hearing you say is that we have this dendritic reaction, and when we're babies, we don't have a… like a boss saying, "Hey, this is the way you should react." So cortisol is telling the body not to do that immediate reaction. So until we have that cortisol our body says, "We don't know if we should react or not. We just have to react because this might be deadly. We don't know yet."
Dr. Naik: Exactly... It's just like it's all hands on deck. We need to protect the body.
Lynita: Sure.
Dr. Naik: So, here's the key challenge though, because, if I was hearing this, I would say, "Okay I'm gonna slather my baby with cortisol as a precautionary measure." And that's what I would be really afraid to advocate for, because what we're talking about here is, one, a mouse study, but two, really low normal levels in your body.
And the way we're thinking about this is not promoting protection through any kind of cortisol or HPA modulation, but targeting those dendritic cells and saying, "Let's shut these guys down." And so that's, I think, where the science and the therapeutic opportunity is.
Lynita: So we don't want to be messing with this developing cortisol system. We really want to come at it from a different angle and say, "Let's calm down the overreaction," rather than... No, I'm not saying that correctly. How do I explain this?
Dr. Naik: Let's shut off the dendritic cells, because the dendritic cell reaction is in the skin. We don't wanna change the whole body. We wanna be really targeted to the skin and limit the disease in the skin.
So if we can really find ways of understanding what the Achilles heel of these dendritic cells is and then shutting them off, I think that could be transformative.
Lynita: I have to ask this question as a parent: is putting corticosteroids on the skin going to mess with the natural development of the immune system?
Dr. Naik: The true answer is I don't think we know how it affects the broader immune system. So this is where I think understanding what's happening in the skin, understanding what's happening with the immune system is gonna require for us to look, because we don't know in human babies, like, how does that affect the HPA, the internal ability, the internal regulation of the cortisol?
So there's a lot that we must learn. And I think especially when you're playing around with steroid hormones, we have to be very careful.
Lynita: Yeah. That's something that parents would really want to know.
Dr. Naik: Now there's other treatment options. Especially toddlers two and up, there are non-steroidal intervention options. So, go talk to your pediatrician and also push for the science and the therapeutic development in this area.
Lynita: Absolutely. Um, on the flip side of that, is there something that parents can do to help support the development of a child's natural immune system?
Dr. Naik: One thing that we do that is really critical to educate the child's immune system is we vaccinate kids, right? And I think vaccines work. I'm an immunologist, I should put that bias out there. I happen to just believe in vaccine science. It's the field I work in. And I think they particularly work when it comes to preventable diseases like measles, and mumps, and rubella, and diphtheria. You know, If we go back 200 years, one in five kids would be dead of these diseases.
And then we developed vaccines, and suddenly that disappeared. So to me, that's the most important thing that anyone can do
Lynita: Sure. And I think with all these diseases disappearing, we also forget how devastating they were.
Dr. Naik: Yeah, absolutely
Lynita: If you could give one piece of advice to a new parent that's worried about eczema or allergies developing, what would your advice be?
Dr. Naik: I always say when in doubt consult your pediatrician. And I would say if your pediatrician is your first stop, don't let it be your last. If there's a persistent rash, ask for a referral to a pediatric dermatologist.
Lynita: Yeah, you are your child's greatest advocate.
Dr. Naik: That's right.
Lynita: My last question that I wanted to ask you is: what do we still need to learn?
Dr. Naik: I want people to understand that the reason we don't know a lot of these answers is because it's not very easy to study and they're very challenging questions that we're only now even beginning to find ways to study it, right? So I think continuing the kinds of studies that we've done that go into how the immune system is working differently and getting into the details of why.
Because then we can develop really powerful therapeutics. But if we never understand those details, we're just gonna be spinning our wheels.
Lynita: Thank you so much, Dr. Naik. It's been wonderful to talk to you and thank you so much for explaining to us what happens in a baby's immune system I'm very inspired by the research you're doing and excited by what it could lead to in the future.
Dr. Naik: Absolutely. Thank you for having me and for all of your advocacy.
