T helper cells are a type of white blood cell that play a central role in regulating the immune system. They are essential for orchestrating immune responses, ensuring proper defense against pathogens, and maintaining tolerance to prevent autoimmunity. But they also play a role in the development of autoimmune disease. They stimulate other white blood cells call B cells to produce antibodies against our self. They also produce chemical messengers called cytokines and chemokines that promote the autoimmune attack. Understanding which T helper subtype is dominant can help determine specific treatment, for both conventional medicines and natural supplements.
Advances in the role of helper T cells in autoimmune diseases
TH-1 Dominance
- Cell mediated immune response – Natural killer and cytotoxic T-cell activity
- Delayed-type hypersensitivity, intracellular pathogens defense
- Patient that “seldom gets sick”
- Tends to go with rheumatoid arthritis, multiple sclerosis, type 1 diabetes, Hashimoto’s and psoriasis.
- Stimulated by IL-12, Tbet transcription factor
- Produces IL-2, TNF-alpha, Interferon-gamma
TH-2 Dominance
- Humoral immune response – B-cell activity
- IgE production, extracellular pathogens, eosinophilic inflammation and the protection for helminthic parasite infection.
- Patient that “is always sick” or has allergies
- Tends to go with systemic Sclerosis, ulcerative colitis, asthma, eczema and lupus
- Stimulated by IL-4, GATA3 transcription factor
- Produces IL-4, IL-5, IL-13, IL-25
TH-17 Dominance
- Respond to fungi, extracellular and gram negative pathogens
- Involved in autoimmune inflammatory disorders
- Require the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation
- Stimulated by TGF-beta, IL-6 and Roryt transcription factor
- Produces IL-17, IL-21, TNF-alpha, IL-22, IL-17F, and CCL20
T-Regulatory
- Responsible for maintaining peripheral tolerance, regulates immune balance, prevents autoimmunity
- Stimulated by TGF-beta, IL-2 and Foxp3 transciption factor
- Produces TGF-beta, IL-10
TH-9
- Antitumor and prevents autoimmunity
- Stimulated by TGF-beta, IL-4 and Stat6 transcription factor
- Produces IL-9
TH-22
- Plays roles in various immune responses and inflammatory conditions, particularly in skin-related diseases
- Stimulated by IL-6, TGF-beta, TNF-alpha, and AhR transcription factor
- Produces IL-22
TH-fh (follicular helper)
- Prevents autoimmunity
- Play a crucial role in regulating B cell responses within the germinal centers of lymphoid tissues, particularly in the context of antibody production and affinity maturation.
- Stimulated by IL-6, IL-21, Bcl6 transcription factor
- Produces IL-6, IL-21, TGF-beta
NKT (Natural Killer T cells)
- Unique subset of T lymphocytes that share characteristics with both conventional T cells and natural killer (NK) cells
- Plays roles in immune regulation, host defense against infections, tumor surveillance, and autoimmune diseases
- Bridge innate and adaptive immunity by rapidly responding to lipid antigens and influencing the activation and function of other immune cells, including dendritic cells, B cells, and conventional T cells.
- Produce IFN-gamma, IL-4
Compounds that stimulate TH-1 (downregulate TH-2)
- Astragalus
- Echinacea
- Berberine
- Andrographis
- Sambucus nigra (black elderberry)
- Mushrooms (beta-glucan, maitake)
- Glycyrrhiza
- Melissa officinali
- Lemon balm
- Mushroom
- Sulforaphane
- Ginger
- Ginseng
- Zinc
- Glutathione
- Vitamin C
- Resveratrol (modulates)
Compounds that stimulate TH-2 (downregulate TH-1)
- Caffeine
- Green tea extract
- Pycnogenol
- White willow bark
- Grape seed extract
- Resveratrol
- Lycopene
- Pine bark extract
- Antioxidants in berries
- Caffeine
- Pycnogenol
- Genistein
- Curcumin (modulates)
- Quercetin (modulates)
- Resveratrol (modulates)
Compounds that downregulate TH17 Dominance
- Probiotics: L. salivarius , L. plantarum
- Curcumin
- Berberine
- EGCG
- Ursolic acid
- Andrographolide
- Black Cumin Seed Oil
- Olive leaf extract [81, 82]
- Fisetin [83] (inhibits IL-17)
- Chinese Skullcap/Baicalin [84, 85] (Number of Th17 and IL-17)
- NAG [86]
- Red Yeast Rice/statins [20] – synergizes with corticosteroids
- Grape Seed Extract [87, 88] (STAT3-)
- Boswellia [89]
- R-Lipoic Acid [90]
- Epimedium/Icariin [91]
- Apigenin [92]
- Honokiol
- CBD [94]
- Galantamine [95, 96, 97]
- Huperzine A [95]
- Butyrate [98] – but increases it in response to an infection [99]
- Cinnamon/NaB [100] (increases IL-17)
- Artemisinin [101]
- Beta-Caryophyllene [102]
- Resveratrol* [103, 104] (conflicting)
- Probiotics: Enterococcus faecalis [105], (Mice)
- Parthenolide [106] – IL-17A [107]
- Ancient Wheat [82]
- Licorice/Lico A [108] (uncertain) [109]
- Ginger extract [110]
