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


  • 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


  • Antitumor and prevents autoimmunity
  • Stimulated by TGF-beta, IL-4 and Stat6 transcription factor
  • Produces IL-9


  • 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


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