The most common immune cells you hear about on the internet is Th1 and Th2 cells however there are many more that can be out of balance in the body and cause major symptoms such as Th9 cells. Th9 cells are the nasty cousins of Th2 cells. They make inflammation worse. They increase mucous production in the body and they worsen allergies and asthma. If you have chronic coughing, sinusitis, lung inflammation, asthma, etc, Th9 cells are likely elevated. So, what do we do when a Th2 dominant person is really flared up and inflamed? One of the keys clinically is to understand that there is likely to be a Th9 co-dominance that is driving the nastier version of the Th2 dominance, worsening the symptom picture.
Getting Technical With The Research…
Below are three papers talking about the importance of Th9 cells in allergic and asthmatic responses and discussing the development of Th9 cells. Below is a summary of what the papers talk about but you don’t need to understand all the biology and immunology of what it all means. I have summarized in a clearer way what to do and what to know about Th2 and Th9 dominance and how to address it.
The first paper, from the Scandinavian Journal of Immunology, discusses the role of Th9 cells in allergic disease. The paper describes microbiome-based pathogens like staph aureus and candida albicans as drivers of Th9 cell polarization. The paper also calls out vitamin D, vitamin A, and butyrate as inhibitors of Th9 expression. What does this mean? the paper indicates that by clearing out pathogenic overgrowth (aka dysbiosis) and supplementing with vitamins D, A and sunbutyrate, you may be able to reduce Th9 dominance and improve the symptom picture for asthmatics and those with allergic-type symptoms.
The second paper, from the Annals of Allergy, Asthma & Immunology, describes the role of vitamin D in a mosaic of inhibitory effects on cytokines we think of as part of the Th2 system. Vitamin D suppresses IL-5, IL-13, and IL-8, but not IL-4. The authors describe the impact of vitamin D as shifting T cells from the more inflammatory Th9 polarization toward Th2. The authors also describe vitamin D as inhibiting interferon regulatory factor 4 (IRF4). IRF4 is known to drive naïve T cells toward Th2 polarization and inhibit Th1 polarization.
The third paper, from Experimental and Therapeutic Medicine, proposes that Th9 cell production occurs via polarization to Th2, again involving IRF4.
The Major takeaways…
There are three main take-home points here. The first is that Th9 cells are the more instense version of Th2 cells. As usual, the more we learn about immunology, the more leverage we get, by seeing further into the patterns. Here, we’re seeing that people with allergies or asthma, which we appropriately think of as classical Th2-mediated disorders are also often Th9 dominant. It appears likely that Th9 dominance expression of the disease process is greater at times of exacerbation.
The second point is that the Th9 component of the disease process can be downregulated by vitamins D and A, by butyrate, and by elimination of pathogens like staph aureus and candida albicans. It’s noteworthy that, as usual, it’s useful to view the overall pattern, to get a sense of the multiple roles that each factor can play. For example, though vitamin D was not observed to directly inhibit IL-4 in the study, it was observed to inhibit IRF4. Since IRF4 is associated with polarization of naïve T cells toward Th2, the indirect effect of vitamin D inhibition of IRF4 would be expected to contribute to downregulation of Th2 cells across time in a free environment (without the constraints of the experimental model). Therefor, by supplementing with Vitamin D to downregulate Th9 dominance, over time you may also be downregulating Th2 dominance too, which is a good thing when you are imbalanced!
The third point is that in many Th2 dominant individuals, we see obvious signs of Th2 dominance, but an absence of eosinophil elevation via bloodwork. Most of these people are already taking high doses of vitamin D, which inhibits IL-5, the driver of eosinophil numbers and activity. But the vitamin D does not inhibit IL-4, the autocrine loop activator of Th2 and driver of mast cell activation. So, the persons mast cells (histamine activators) continue to over function, the person continues to have histamine sensitivity, allergy, etc., but in the absence of eosinophil elevation. SO to recap, when someone has lab work done and their doctor says their eosinophils are low, they can still be very much inflamed and Vit D supplementation could be what is lowering eosinophils but allowing mast cell activation to proceed.
All of this is consistent with other immunological factors we’ve discussed, including the fact that alterations in the intestinal microbiome can drive epithelial cell inflammation (lungs and gut), which drives the production of Th2 polarizing cytokines.
What To Do To Reduce Th2 and Th9 Immune Cells
- Reduce Th9 cell production with vitamin D, Vitamin A and sunbutyrate
- Supplement with reishi and/or chaga mushroom to support Th1 cell production as well as berberine and NAC
- Take antihistamines such as quercetin and vitamin C to reduce mast cell activation
- Clear out pathogens from the body with a candida and parasite cleanse
- Include lung, liver and kidney drainage (see protocols on this platform) to open the emunctories
- Remove sugars, starches and inflammatory foods including alcohols and processed foods
- Include lobellia, magnesium glycinate and curcumin for extra lung/allergy support
*All supplements can be found on puremarket.ca!!*
Research Articles Cited
Th9 Cells in Allergic Diseases: A Role for the Microbiome?
Scand J Immunol. 2020 Apr;91(4):e12857. Badolati I, Sverremark-Ekström E, van der Heiden M.
Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma
Ann Allergy Asthma Immunol. 2014 Feb;112(2):154-62. Keating P, Munim A, Hartmann JX.
Th2 cells as an intermediate for the differentiation of naïve T cells into Th9 cells, associated with the Smad3/Smad4 and IRF4 pathway
Exp Ther Med. 2020 Mar;19(3):1947-1954. Abdelaziz MH, Wang H, Cheng J, Xu H.