The best leverage we have to regulate autoimmunity is to influence the way your T-cells mature and differentiate. This goes far beyond simply blocking the downstream effects of inflammation, which is what most pharmaceuticals do. Instead, this approach goes further upstream, to influence the type of T-cells that get made from the get-go. Here we explain the why and how behind this approach. By the way, this is the same approach we take for destructive types of inflammation that are not currently categorized as autoimmune, including osteoarthritis, osteoporosis, and endometriosis.
T-cell differentiation 101
This refers to the ways that your naïve (“baby”) T-cells develop into different types of mature (“grownup”) T-cells. Think of your naïve T cells as blank slates that can mature in different and separate directions. These mature T-cells drive specific immune messengers (cytokines) in order to perform distinct immune tasks. They can mature into regulatory T-cells (Treg) or into effector T-cells. Simplistically put, Tregs suppress inflammation and effector T-cells stimulate inflammation. The effector T-cell phenotypes we are concerned with here are Th17, Th1, and Th2. To streamline and animate this topic, we’ve given personalities to these mature T-cell phenotypes:
Ideally, your naive T cells can mature in any direction as needed, because there are purposes for each type. The problem is when you get stuck, or dominant, in one direction – especially the Th17 troublemaker or the Th2 overprotector. For autoimmunity, we generally want to downregulate these two personalities and upregulate the Th1 warrior and T-reg peacemaker. There are steps to doing so, which we discuss next.
Orchestrating T-cells for autoimmunity
Let’s get to know the personalities in the mix:
We call Th1 the warrior because it’s your main defense system. Th1 cytokines fight viral and bacterial pathogens, guard against cancer cells, and directly suppress autoimmunity. Th1 can be upregulated in an acute infection, however, in chronic illness and autoimmunity, it’s typically downregulated. These are the people with chronic autoimmune flares, poor surveillance against cancer and atypical cells, and poor defense against infections. These folks are the ones that catch all the viruses that go around and get hit hard by them. We upregulate Th1 with the researched nutrients baicalin, berberine, sulforaphane, echinacea, and glutathione, as well as lifestyle factors such as adequate sleep.
Th2 drives cytokines that respond to “hollow space” inflammation and irritation. This includes the nasal passages, lungs, intestinal tract, bladder, and vagina. These spaces are similar in that they are open to the outside world, and irritants like allergens or microbes can cause local inflammatory reactions in the mucosal linings of these spaces. Other situations that drive a Th2 response include neuroinflammation, stress chemistry, and toxins.
Th2 cytokines drive more Th2 cells, so this response can easily become chronic, especially when whatever is perpetuating it is chronic. People become stuck in persistent Th2 cytokine production, hence the name over-protector. Excessive perceived stress, histamine, sinusitis, asthma, interstitial cystitis, gut dysbiosis, mold intolerance, post-Covid brain fog, and cognitive impairment after a concussion are examples of this persistent Th2 over-protector response. These are the people who are overly sensitive to things in their environment, including foods, odors, and allergens.
A big concern is that the Th2 over-protector blocks your Th1 warrior response. People with chronic autoimmunity and inflammation typically already have a dampened Th1 warrior response. When you lose your warrior response, your ability to fight infections, suppress autoimmunity, and target cancer cells is suppressed. We can relax the Th2 over-protector with astragalus, quercetin, luteolin, oxymatrine, and perilla, and lifestyle interventions with healing food plans and management of perceived stress. You can do this at the same time that you support the Th1 warrior.
Th17 is nicknamed troublemaker here because it drives the highly destructive inflammatory cytokines that cause tissue breakdown in autoimmunity and conditions like osteoporosis. With chronic autoimmunity, we definitely want to calm down the Th17 troublemaker and keep it in check. We do this by reducing inflammatory triggers because any type of chronic inflammation can feed Th17. We also support the Th1 warrior and Treg peacemaker, because both suppress Th17. When we hunt for inflammation, we can look for the types that activate the Th2 over-protector above, and we can also look for hidden inflammatory triggers such as blood sugar and hormone imbalance, overtraining, or stealth infections like Epstein Barr virus or gut pathogens. The best means to calm down the troublemaker is to heal and clear sources of inflammation plus strengthen the warrior and the peacemaker. In that order.
T-reg cells block all the effector T-cells, including the Th17 troublemaker. They help your immune system become tolerant, hence the name peacemaker. Often tolerance is a good thing, especially for autoimmunity. However, sometimes tolerance goes too far. You don’t want to become too tolerant of cancer cells and pathogens. So while it’s a great idea to support the T-reg peacemaker to block the Th17 troublemaker, it’s also going to block the Th1 warrior which is typically already downregulated with chronic autoimmunity and inflammation. So FIRST support the Th1 warrior and THEN support the T-reg peacemaker with the nutrients curcumin, resveratrol, vitamin D, and omega-3 DHA and EPA. Lifestyle support includes exercise, love and connection, breastfeeding, and regular circadian rhythms.
Putting these steps into action
I first learned about T-cell differentiation and the information I’m presenting here in 2019 when I began my in-depth coursework in functional immunology. I’ve now had years of assessing patients’ T-cell status and applying successful protocols to help get autoimmunity into remission. This approach works!
Here’s a visual of the steps:
Let’s nix the Th/Th2 autoimmune disease hypothesis
You may have read or heard that certain autoimmune diseases are “Th1 dominant” or “Th2 dominant.” If you follow this theory, you may be quite confused by this article. This hypothesis is based on old information from the early 2000s. Yes, in the emerging field of immunology, our knowledge changes all the time, so theories from the early 2000s can be old and out of date. We now know that chronic autoimmune diseases are not Th1 or Th2 driven. This is out of date and does not reflect what we now know about immunology.
Is this topic interesting to you? I’d love to hear your questions and comments below. Stay tuned for more posts that include the labs and questionnaires I use with my patients.