If you have an autoimmune disease, this topic likely isn’t completely new to you. Many autoimmune authorities have blogged on this topic: Datis Kharrazian, the Paleo Mom, the women behind Autoimmune Paleo (AIP), Selfhacked.com, and many more. However, as the scientific community comes to understand these cells better, these old books, blogs, and podcasts have become outdated and perhaps even harmful.
I’m here to clear up the confusion surrounding this topic.
What are TH1 and TH2 and why are they important?
TH1 and TH2 are two types of T Helper cells, which are part of the adaptive immune system. Currently there are at least 7 different types of T helper cells, but TH1 and TH2 are the ones we’ve known about the longest. These two cells have a unique relationship: When one “goes up” (is stimulated) it suppresses the other one- that’s why they’re generally drawn on two ends of a seesaw like this:
The myth of TH1/TH2 balance and autoimmunity
For about 20 years, scientists and healthcare professionals have believed that perfect seesaw balance is ideal. In this model, autoimmunity results from imbalance in this scale. If TH1 is “too active” (notice, quotes), it is said that an autoimmune disease is “TH1 dominant” and vice versa. There are lists on the internet and in print that list diseases as either TH1 or TH2 dominant, but this is horribly over simplified and incorrect. For many years this idea has been perpetuated by blogs, books, podcasts, and doctors, several of whom I have listed above. But what if this way of thinking was over-simplified, incorrect, and possibly harmful?
TH1 cells are not the bad guys: they were framed
Many websites and books list the so-called “TH1 dominant diseases;” the vast majority of autoimmunity is still thought of this way. However, we now know that this is simply not accurate.
Much of the earlier research on TH1 cells actually focused on one of the chemicals/cytokines the cells make: IL-12. Drugs that target half of the IL-12 molecule have shown promise in treating autoimmunity, which further strengthened the “TH1 = bad” hypothesis.
Then in 2006 scientists discovered a new TH cell: TH17. These guys are everything your mama warned you about- they are nasty ombres and play a central role in both autoimmunity and cancer. Unfortunately for TH1 cells, their cytokine (IL-12) and it’s receptor share a portion/subunit with the TH17 cytokine IL-23. It was this subunit (P40) that was targeted by those drugs and showed promise. For years, TH17 cells swam around undetected because we didn’t know to look at the other half of a receptor!
What are their purposes? What do these cells “help,” anyway?
Every cell and chemical in your body has a good reason to be there. The reason these cells are called “helpers” is that they instruct other cells. TH1 and TH2 (and the other T helpers) instruct the rest of your immune system to efficiently do their jobs. I like to think of these cells as mafia bosses, and the rest of the cells are their goons.
“High” or “low” for a reason
If one side is high or low, I believe it is for a reason, and that reason is 100x more important than the seesaw itself. If TH2 is more active, for example, it might very well mean you have a parasite. If someone is more TH1 polarized, this may be perfectly fitting for their current situation if they happen to have a viral infection. To make matters more complicated, many infectious agents (viruses, mold, parasites, bacteria) have the ability to suppress our immune systems in a way that allows them to survive longer. Viruses and fungi, for example, both have suppressive effects on TH1-mediated immunity, particularly in the long-run. This allows the pathogen to more easily become a chronic infection.
This is where the old model really falters: perfect balance is NOT desirable. The ability to clear your current infection(s) is the most desirable place for any of us to be. This is particularly true of autoimmune disease patients, who are nearly always infected in some way. Once more, by perpetuating this myth for so long, I believe that healthcare professionals and bloggers inadvertently did great harm. Those overly-simplified and incorrect lists have surely steered many people away from the very herbs and supplements that could help them finally heal.
It is worth saying, however, that if you don’t have autoimmunity and you are not infected, then having a perfectly balanced (and flexible!) seesaw is a fine goal.
How to tell if you’re TH1 or TH2 dominant. This will include the merits and pitfalls of lab testing. (Link to the article)
References to some of what I talked about (for the geeks out there)
1. Hoeve, M., Savage, N., Boer, T. D., Langenberg, D., De Waal Malefyt, R., Ottenhoff, T., & Verreck, F. (2006). Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. European Journal of Immunology, 36(3), 661-670. doi:10.1002/eji.200535239
2. Cooke, A. (2006). Th17 Cells in Inflammatory Conditions. The Review of Diabetic Studies, 3(2), 72-72. doi:10.1900/rds.2006.3.72
3. Teng, M. W., Bowman, E. P., Mcelwee, J. J., Smyth, M. J., Casanova, J., Cooper, A. M., & Cua, D. J. (2015). IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases. Nature Medicine, 21(7), 719-729. doi:10.1038/nm.3895
4. Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006). Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties. Immunity, 24(6), 677-688. doi:10.1016/j.immuni.2006.06.002
5. Harrington, L. E., Mangan, P. R., & Weaver, C. T. (2006). Expanding the effector CD4 T-cell repertoire: The Th17 lineage. Current Opinion in Immunology, 18(3), 349-356. doi:10.1016/j.coi.2006.03.017
6. Kelchtermans, H., Billiau, A., & Matthys, P. (2008). How interferon-γ keeps autoimmune diseases in check. Trends in Immunology, 29(10), 479-486. doi:10.1016/j.it.2008.07.002
7. Lees, J. R. (2015). Interferon gamma in autoimmunity: A complicated player on a complex stage. Cytokine, 74(1), 18-26. doi:10.1016/j.cyto.2014.10.014
8. Kosco-Vilbois, M. (2003). Faculty of 1000 evaluation for Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. F1000 – Post-publication Peer Review of the Biomedical Literature. doi:10.3410/f.1011192.185624
9. Burkett, P. R., Horste, G. M., & Kuchroo, V. K. (2015). Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity. Journal of Clinical Investigation, 125(6), 2211-2219. doi:10.1172/jci78085
10. Lee, G. (2018). The Balance of Th17 versus Treg Cells in Autoimmunity. International Journal of Molecular Sciences, 19(3), 730. doi:10.3390/ijms19030730