Th2 cytokines

Th2-cytokines are the interleukins: IL-4, IL-5, IL-13, IL-22 and the inducing cytokine TSLP (thymic stromal lymphopoietin).

The defense mechanisms of the immune system are divided into an innate (natural) immune response directed against all substances recognized as foreign to the body and an acquired (adaptive) one, in which antigen-specific cells and antibodies against specific allergens/antigens/pathogens are produced. In both systems complex, mutually influencing and regulating cell populations are active and dependent on the type and structure of the antigens. Both defence systems each have a cellular and humoral component.

The type of reaction with which the immune system responds to an antigen is influenced by various activating and inhibiting factors. These include the type and quantity of the antigen, the specifics of the lesioned tissue (epidermis, respiratory tract, gastrointestinal tract, the way the antigen is presented and the cytokine pattern expressed.

Antigen presenting cells (APC), but also other effector cells of the immune response are responsible for the cytokine pattern, which is characteristic for an adequate immune response. These stimulate and shape different T-cell subpopulations and thus their (specific) cytokine responses.

If an antigen-presenting cell (APC) in lymphatic tissue meets a naive T-cell (a cell that has not previously had antigen contact), it differentiates functionally into a CD4-positive T-helper cell (Th0) after activation by the APC.

According to our current understanding, Th0 cells can differentiate into Th1 and Th2 lymphocytes in 2 subgroups. Th1 and Th2 lymphocytes produce a different cytokine spectrum with different functions.

The Th2 immune response plays a dominant role in atopic diseases. It is characterized by the cytokines interleukin-4, interleukin-5, interleukin-13, interleukin-22. These cytokines are also called Th2 cytokines.

Ultimately, the question of which factors are responsible for Th2 polarization remains unanswered. TSLP, the "thymic stromal lymphopoietin", a cytokine related to interleukin-7, which is massively produced by keratinocytes from lesional atopic skin, plays a key role in this process. Also the innate ILC2 cells, "innate lymphoid cells" of atopic persons, are able to secrete large amounts of Th2-cytokines after stimulation.

Furthermore, the interleukin-25 produced by keratinocytes, as well as the interleukin-33 produced by macrophages, mast cells and epithelial cells can lead to a Th2 immune response. They are also involved in the simultaneous activation of mast cells and basophilic granulocytes (histamine release). Even pollen allergens seem to pave the way for a Th2 immune response by blocking interleukin-12 production from dendritic cells via certain prostaglandin-like lipid fractions (so-called phytoprostanes) of pollen.

Thus, the Th2 cytokine pattern is a product of predisposition, specific activating immune reactions and inhibitory influences that shift the finely balanced immune balance towards the Th2 immune response.