Introduction to T Helper Cells 17 (Th17) and Interleukin-17

T helper cells start off ‘naive’ T cells and can turn into  Th1, Th2 or Th17 cells.

A naive T cell can either become an inflammatory Th17 cell or an anti-inflammatory Treg cells.  The goal for people with Th17 inflammation is to convert more of these cells to Treg cells.

Technical: Cytokines or the lack of them influence which cell the naive helper cell will convert into. The two necessary cytokines are TGFb and IL-6, which I’ve spoken about.  IL-6 (some say IL-21) is what ultimately determines if it turns into an inflammatory or anti-inflammatory cell.   IL-23 is a cytokine that determines if these Th17 will cause disease (R).  IL-1β can also increase the production of Th17 cells. (R)

Th17 cells produce the cytokine IL-17, as well as TNF  and others (R).

IL-17 increases kynurenine (so does cortisol, IL-1, TNF and IFNy/Th1 dominance) (R).  This was found to be elevated in IBS (R). Overall, increasing this pathway probably isn’t a good idea, although the effects are mixed (R).  It increases oxidative stress and leads to depression..

Kynurenine can then turn into kynurenic acid or quinolinic acid.  Kynurenic acid blocks NMDA, AMPA, glutamate and nicotinic receptors, all of which are important for learning and memory.  Thus, Kynurenic acid can make us dumber (R). Inhibiting Kynurenic acid can result in cognitive enhancement (R).

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Interleukin 17 acts synergistically with TNF and IL-1. (R) (Not a word, but it should be. It means the opposite of synergistically.)

IL-17 is commonly associated with allergic responses. IL-17 induces the production of many other aspects of inflammation such as IL-6, IL-1β, TGF-β, TNFIL-8, MCP-1, and PGE2) from many cell types. The release of cytokines causes many negative events such as airway narrowing in people with asthma (by fibrosis). (R)

Th17 cells have a circadian rhythm.   The amount of Th17 cells changes during the day-night cycle.  The production of Th17 is higher at midnight than at noon. (R)

Th17 and IL-17 aren’t bad in all ways.  Th17 has a protective role in combating fungi (R) and some bacterial infections (‘extracellular’) (R).  Tregs also help combat bacteria (R).   Increased Th17 may also be anticancer in some ways (R).  There is a well-known cancer and autoimmune trade-off spoken about in the literature.

Researchers also found that in people with food allergies (classical type), IL-17 production was impaired, but not in healthy people.  The study found IL-17 was a potential biomarker for tolerance to food antigens. (R)

Normal IL-17A levels are 0.89 pg/ml.  In people with mild sleep, apnea levels are 1.02 pg/ml, in moderate sleep apnea 1.18 pg/ml, and in severe sleep apnea 1.62 pg/ml. (all median values) (R).

Th17 cells appear to be resistant to the suppressive effects of Tregs (R, R).

Males vs Females

Women are also more susceptible than men to develop a host of autoimmune conditions, including Multiple Sclerosis (female to male ratio of 2:1), Rheumatoid Arthritis (2:1), Systemic Lupus Erythematosus (9:1), Sjogren’s syndrome (9:1), and Hashimoto’s thyroiditis (9:1) (R).

The higher female prevalence of these diseases may be related to the fact that women develop more robust immune responses than men (R).

Women have higher levels of Th1 cells, IgM and CD4+ cell counts, and show stronger immune response responses to vaccinations (R).

Females are more prone to Th1 dominance, while males are more prone to Th17 dominance (R).

This is because Androgens increase PPAR alpha, which cause inhibition of Th1 dominance.  At the same time, men have lower PPAR gamma, which leads to Th17 dominance (R).

To some extent, Th1 and Th17 ‘compete’ with each other.  IL-2 produced by Th1 cells activates STAT5, which competes with STAT3 (which produces Th17 dominance) (R).

Supporting this, castration of male mice enhances Th1 autoimmunity and lowers Th2 cytokine production (R).

Diseases Associated With Increased Th17

Th17 is lower in chronic fatigue syndrome (R), but I don’t see how this contributes to it.

Studies in animal models of MS suggest that Th1 cells are important in initiating acute attacks, while Th17 cells are more important in mediating progression of this disease. Consistent with this, IL-17 is expressed at higher levels in chronic versus acute MS lesions (R).

Why Some People Do Worse With Higher Protein, Kombucha

Th17 can explain why a bout of chronic stress can result in autoimmune issues.

Th17 can also partly explain why some do worse with a higher protein diet when they’re inflamed.  This is because Tryptophan, and Arginine to a lesser extent, can increase Th17.

Other amino acids can activate mTOR, which increases Th17 immunity.

Kombucha decreases Th17 cells, but can increase IL17 release, which is just as bad as increasing Th17, because the negative effects are mediated through the cytokines.

Circadian disruptions increase Th17 cells, while tanning in the sun strongly inhibits this response.  This could help explain why people who live further from the equator are more likely to get autoimmune diseases.

Also, paleo diets have more Zinc, Vitamin A and D3, which can help reduce Th17 immunity.

How to Inhibit Th17 and IL-17 

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Usually, substances that inhibit Th1 cells also inhibit Th17 cells.  There are some exceptions.

IL-17 is one of the main cytokine released by Th17 cells, so inhibiting this cytokine blocks most or all of the damage caused by these cells.

There are two proteins that allow the cytokine IL-17 to be produced: STAT3 and Nf-kB (R).  I wrote how to inhibit Nf-kB and I describe below how to inhibit STAT3.

Lithium only inhibits Th1 but not Th17 (R).

Lifestyle to inhibit Th17

Diet to inhibit Th17

  • Avoid lectins* (R)
  • Fish oil (R)  (reduced the surface expression of both IL-6R and IL-23R)
  • Broccoli sprouts/Sulforaphane (R),
  • One meal per a day (in response to LPS) (R)
  • Coffee (R)
  • Kombucha/Lactic acid (R) –  although it increases IL-17A, the cytokine released by this cell.

Nutrients to inhibit Th17

Hormones/NT’s to inhibit Th17

Supplements to Inhibit Th17/IL-17

Drugs That Inhibit Th17

Pathways to inhibit Th17

These actions inhibit Th17:

Factors That Increase Th17 Immunity that You Should Avoid

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Lifestyle

  • Chronic psychological stress/anxiety.  In a sentence, chronic stress causes cortisol/glucocorticoid ‘resistance’ (R).  The implications are that your autoimmune/inflammatory issues will worsen before you start to improve when you reduce stress.  This means that a higher level of cortisol is needed to suppress the immune system.  Stress causes epinephrine to be released and helps cause a dominant Th2/Th17 profile. Therefore, stress can affect inflammatory conditions by favoring Th17 immunity. (R)  Cell cultures from anxious individuals showed Th17 dominance.  These people produced higher amounts of IL-17 and TNF.   In healthy people, glucocorticoids/cortisol decreased excessive Th17 activation, but not in highly stressed people. The anxious people became insensitive to glucocorticoids. (R)  Also, adrenaline, which is a Beta2-AR agonist, aggravates IL-17-type immune response. (R)  Asthma drugs also worsen this response and these drugs are associated with disease progression (but they offer temporary relief).
  • Marathons/Excess exercise (R).  I caution against excessive exercise in general.
  • Obesity (R)
  • Circadian Rhythm disruption (R),
  • EMFs (R)

Diet

  • Gluten (R),
  • Cholesterol (desmosterol) (R) (not necessarily influenced by dietary cholesterol)
  • Iodine excess (R) – moderate to high.  Extremely high levels results in Th1 elevation (R).  There’s a fad in the alternative health community to take excessive iodine.  I don’t agree with this approach, even if some people claim it helped them.  Make sure you aren’t Th1 dominant.   I take about 400mcg of supplemental iodine a day and recommend this to most people.
  • Tryptophan (by deactivating IDO) (R, R2)
  • Arginine (R)
  • Frying oils/Smoking (both produce oxysterols) (R). Also, the enzyme CYP27A1 turns cholesterol into bile and this enzyme can increase oxysterols and therefore Th17 dominance (R)
  • High salt diet (R) – there’s a high salt fad in the alternative health community.  Just make sure you’re not Th17 dominant before you start going crazy with salt.
  • Long chain fatty acids (R)

Toxins/Infections

  • Free radicals (R)
  • Fungal infections (R)
  • Viruses
  • Intracellular and extracellular bacteria (R)
  • Parasites (R)
  • Heavy Metals: Cadmium, Mercury and probably Lead and Arsenic (R)
  • Flu Viruses (R)
  • Klebsiella pneumoniae, Citrobacter rodentium, Candida albicans, Listeria monocytogenes, Salmonella entericaMycobacterium tuberculosis (R)
  • Chlamydia (R)
  • Certain gut microbes (R)

Hormones

Supplements

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  • Forskolin (R)
  • Uric acid (in combination with IL1b and IL18) (R)
  • Resveratrol (R) – contradictory
  • NAD+/Niagen NAD. Although it increases both Th1 and Th17 cells, it decreases their ability to cause disease (R)
  • Butyrate (R) – in response to LPS.  However, it increases Tregs (R).
  • L Casei (R), S Boulardii (R), Bacillus Subtilis (R) – increases IL-17.

Pathways

Genes and Th17

These genes are associated with Th17 immunity.

STAT3 Inhibitors Are Critical To Decreasing Th17 Cells

STAT3 is a protein that binds to DNA and increases gene expression.

STAT3 is essential for the production of the TH17 cells, so if you reduce this protein, Th17 cells inevitably decline (R).

Unsurprisingly, STAT3 plays an important role in autoimmune and inflammatory diseases and some cancers.

See more about STAT3 and a list of natural inhibitors.

mTOR  Inhibitors Are Critical To Decreasing Th17 Cells

Increased mTOR promotes Th1 and Th17 immunity, leading to increased intestinal inflammation (R), among other issues.

mTOR increases another protein called hypoxia-induced factor (HIF)-1α, which increases Th17 cells. (R)

Inhibiting mTOR is a significant pathway to decrease Th1 Cells.

This is a good picture that shows you the conditions needed for these four T Cells.

Technical: mTOR increases glycolysis, which is what allow Th17 cells to proliferate. This works through HIF1α. Blocking glycolysis inhibited Th17 development while promoting Treg cell generation. (R)

Read this post on how to inhibit mTOR.

Images

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Disclaimer and Caveats

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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29 COMMENTS

  • John

    Promote means you should do it/take it, it’s good for reducing TH17

  • Ella

    I have vitiligo and alopecia plus u have been taking metdormin for over 10 years. Does this mean i can gave an elevated th17. What can i do to lower it.

  • Nick Stojanovich

    Lifestyle to inhibit Th17
    Avoid stress I understand this also I understand avoiding strenuous excercise
    Why no Sun or nitric oxide

  • Dani

    I have psoriasis and multiple sclerosis. My best goals are: Not to eat gluten and to respect circadian cycles strictly 7 days a week.

    I find the information in this article very useful. Thank you very much!

  • surfinthetao

    Joe, thanks for your site. If you ever want to do a piece on interstitial cystitis, contact me, maybe we can put some interesting pieces together for some people. I also have an idea for an IC supplement.

    I am a sufferer of interstitial cystitis, and histamine seems to be related to (IC). I noticed I do well on these supplements listed in this article, as well as many of the IL-6 inhibitors you mentioned on your site, which this study links to bladder problems.

    HB-EGF, and APF could be other factors for investigation that the study below talks about.

    New theories in interstitial cystitis
    Nature Clinical Practice Urology (2004) 1, 85-89
    doi:10.1038/ncpuro0057
    Received 3 August 2004 | Accepted 2 November 2004

    Carnosine seems to help, which could be partly due to reduction of crosslinking of collagen from AGE’s? and somehow related to RAGE, the receptor for advanced glycation endproducts, and the bladder’s protective glycosaminoglycan (GAG) layer? type 1 and 3 collagen seemed to help for awhile, but then i broke out, although type 2 seemed help a bit with no symtoms.

    A lot of information from a lot of experimentation maybe you could put together.

    -J

  • LP

    I’m very interested reading this. I suffer from psoriasis, and it seems very promising new treatments work by inhibit IL-17. If taking ursolic acid also inhibits IL-17… has anyone tried this for psoriasis? Would it work?

  • Kimberly Lohr

    you say what can inhibit but then says )promote). But those are opposite actions … I’m confused but want to help myself since I have autoimmune disease.

    1. Nattha Wannissorn

      The (Promote) means you should take it.

    2. Alaina

      I was rather confused as well. Thanks for asking this question! The author should have specifically stated the definition, instead of ambiguity in parentheses.

  • drbiagiandrea

    Hi
    i have a question about exercise and autoimmune disease:
    if to lower Th1 i have to do high intensity exercise(yuo write in article about Th1) why to lower Th17 i have not to do high intensity exercise since some autoimmune disease have both Th1 Th17 culprit

  • Thalassa

    Hi Joe,

    Why is resveratol under both the supplements that inhibit and supplements that increase lists?

    1. Joseph M. Cohen

      contradicting studies

  • Mikey

    Notice you didn’t have Hydrangea on your list- used it as a tea for a month (alongside Kalawalla for TH1/TH2 balancing properties that blew Black Seed Oil out of the bottle) and my appetite, weight and energy are soaring with great sleep and enhanced recovery from workouts. The T.U.L.I.P protocol doesn’t leave me dumb the day after I use it anymore either.

    1. Guy

      What is TULIP Protocol.?

  • Omega Terus

    What does it mean when someone has super-low Interleukin-17? I’ve done a blood cytokin profile lab test and everything is kind of normal, except IL-17 is super low, like below detection threshold which is 3.2 pg/ml. Reference range is 49-446. Th1/Th2 ratio is 3.7 (ref. range 3.5-11.0), so Th1 is on the low side, but just barely. But the IL-17 is surprising. Also my hs-CRP was 16.7 mg/l (with ref < 3.0, so inflammation). Test where done at IMD-Berlin in Germany at 11:15 AM after a good night's sleep of about 9 hours, woken up around 8 AM without alarm clock (Th-17 has a daily cycle).

  • Mikey

    Hi Joe,

    Would a Th17 dominant person exhibit the same inability to gain wight as occurs in Th1? Would it be a gesture between the two?

  • Ramona

    Thats interesting i have a question regarding curcuma. My doc prescribed it for hashimotos I also have celiac disease but I also read it stimulates th2 and I’d rather inhibit th17 to be one the safe side can you give me your opinion?

  • Erika

    Great article! Thanks!
    I was just wondering how one knows whether their Th17 is too high… I had some blood tests done for Th1 Th2 and Th17 (expressed in percentages) but I have no idea how to interpret the results, as there are no reference values, and I cannot seem to find them clearly on the internet either… The only value I found was in an article that stated that average Th17 in healthy individuals is around 0.8%. If mine is 2.2% is that considered high? Thanks for your time!

    1. Joseph M. Cohen

      It’s not the number of cells that’s most important – it’s the level of cytokines that they produce. It’s their activation. You need to get the test that I recommend done.

      1. Erika

        Oh, ok! Thanks!

  • Phil

    Would you recommend progesterone for guys? Am dealing with what I believe is “progesterone steal” atm.

  • daz

    hi Joe,

    the Ref link at the end of the following text seems to be missing;


    Technical: mTOR increases glycolysis, which is what allow Th17 cells to proliferate. This works through HIF1α. Blocking glycolysis inhibited Th17 development while promoting Treg cell generation. (R)

    1. Joseph M. Cohen

      Thx, fixed

  • DdR

    Hey Joe, how does one get tested if he or she is a resident of the great state of New York like yourself?

    1. Joseph M. Cohen

      There are Labcorp and Quest centers just across the border into CT.

      Labcorp and Quest tests can not be drawn in NY, NJ, Mass. and RI.

      Didn’t hear from you in a bit. Are you keeping to a lectin avoidance diet?

  • MachineGhost

    > Some will argue that the value is close to zero, such as the religious
    > group called “Science Based Medicine“, but I obviously disagree with
    > this position. I will write a post on SBM and how they think they’re
    > skeptical and rational, but aren’t. The organization reminds me of the
    > closed mindedness of many religious groups.

    They’re no different than the James Randian skeptics, the Stephen Barrett groupies or the high IQ Mensan blowhards. They’re naive cultists and are probably hard-wired in the brain as Republicans (i.e. oversensitive to in-group dangers from out-groups, but blindly support in-group crony capitalism ideologically). What’s especially galling is them hiding their cultism behind “Science” to cause a cognitive breakdown in anyone that attempts to pull their heads out of their asses. I look forward to your post about them.

    1. Joe

      Lol

  • Dave Fellows

    Great post. This series on inflammation has been very interesting and useful – thanks!

    1. Joe

      Thanks!

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