Cytokine Atlas


T Helper 2 (Th2) Cells & Cytokines

Th2 cells mediate the activation and maintenance of the humoral, or antibody-mediated, immune response against extracellular parasites, bacteria, allergens, and toxins. Th2 cells mediate these functions by producing various cytokines such as IL-4, IL-5, IL-6, IL-9, IL-13, and IL-17E (IL-25) that are responsible for strong antibody production, eosinophil activation, and inhibition of several macrophage functions, thus providing phagocyte-independent protective responses. These cytokines also counteract the Th1 responses that allow for the Th2 responsiveness to IL-4. IL-4 signals through STAT6 to upregulate GATA3 expression, the master regulator of Th2 cell differentiation. Repression of this activity results in the development failure of IL-4 producing cells. IL-4 also suppresses Th1 and Th17 cell responses through the upregulation of transcriptional repressor(s) of IFNγ and IL-17 production. However, the IL-4/STAT6 pathway is not completely essential for Th2 cell differentiation as Th2 cell differentiation can also occur through other cytokines such as TSLP, IL-17E (IL-25), and IL-33. Regardless, GATA3 expression and STAT5 activation, most commonly through IL-2 for Th2 cells, is completely essential for Th2 cellular differentiation.

Functionally, Th2 cytokines have effects on many cell types in the body as the cytokine receptors are widely expressed on numerous cell types. Th2 cells stimulate and recruit specialized subsets of immune cells, such as eosinophils and basophils, to the site of infection or in response to allergens or toxin leading to tissue eosinophilia and mast cell hyperplasia. They induce mucus production, goblet cell metaplasia, and airway hyper-responsiveness. Th2 cells also control the regulation of B cell class-switching to IgE. Because of their influence on the production of antibodies and allergic responses, over activation of Th2 cells appears to be responsible for the exacerbation of allergies (Type-1, immediate hypersensitivity reactions), autoimmune reactions such as chronic graft-versus-host disease, progressive systemic sclerosis, and systemic lupus erythematosus. Additionally, Th2 cells are also known to be responsible for the development of asthma and other allergic inflammatory diseases. Interestingly, Th2 cells also produce the growth factor amphiregulin and IL-24 which have anti-tumor effects.

Th2 Cell Differentiation

Th2 Master Regulator of Differentiation

GATA3

Th2 Differentiation Profile

IL-2

  • Expressed by activated T cells
    Mediates their proliferation and clonal expansion

IL-4

  • Required for Th2 priming and maturation
  • An autocrine of Th2 cells during their maturation
  • High concentrations can block the generation of Th1 cells from naïve T cells

IL-6

  • Released by APCs
  • Initiates maturation of Th2 cells from TH0 in conjunction with IL-4
  • High concentration can block the generation of Th1 cells in a similar fashion to IL-4

IL-17E (IL-25)

  • Induces cytokine expression
  • Helps maintain Th2 function
  • Plays a critical role in the formation of Th2 memory

IL-31

  • Expressed by activated CD4+ cells
  • Associated with enhanced IL-4 and IL-13 expression by TH2

IL-33

  • Necessary for Th2 cytokine production

Th2 Secreted Cytokine Profile

Amphiregulin

  • An EGF family member growth factor with anti-tumor effects

IL-3

  • Assists in the recruitment and maintenance of basophils into lymphoid tissues in response to infection

IL-4

  • Inhibits the proliferation and differentiation of Th1 cells
  • Stimulates B cell proliferation and maturation into plasma cells
  • Regulates the class switching of antibodies
  • Increases IgE production

IL-5

  • Attracts and activates eosinophils

IL-6

  • Critical role in B cell maturation into IgG secreting cells
  • Plays a significant role in inflammation and autoimmunity

IL-10

  • Inhibits secretion of various cytokines by Th1 cells, macrophages, and dendritic cells

IL-13

  • Stimulates B-cell production of IgE
  • Attracts basophils and mediates the release of granules
  • Triggers mast cells to release granules

IL-17E (IL-25)

  • Co-mediates production IL-4, IL-5 and IL-13

IL-31

  • Implicated in inflammatory responses in the skin
  • Recruitment of PMNs, monocytes, and T cells to the sites of infection

Th2 Cell Marker Profile

Th2 Maturation Blocked By

Th2 Cell Cytokines
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