Alarmin IL-33 is constitutively expressed as a nuclear protein in all epithelial and endothelial cells, but also in secondary lymphoid organs.

[11] Releasing of this cytokine is associated with necrosis or mechanical damage of epithelial or endothelial tissues caused by injury or inflammation.

The membrane-bound ST2, which provides the activation pathway and soluble ST2 that originates from another promoter region of the il1rl1 gene and lacks the transmembrane and cytoplasmic domains.

IL-33 binds specifically to ST2, which in association with IL1RAcP to form a heterodimeric receptor and TIR domain dimerization together with MyD88 leads to activation of TRAF6.

Foxp3 transcription factor is necessary for T regulatory cell phenotype stability and suppression function mainly based on gene silence effect.

It was also shown, that after different cytokine IL-23 stimulation which leads to activation of STAT3, the suppressive effect of Tregs is decreased together with ST2 and Foxp3 expression.

[15] This observation suggest longterm theory about crucial role on antagonistic aims of IL-33 and IL-23 to mucosal immunity and in their productions are able to cause IBDs.

[16] It is well known, that high presence of T regulatory cells in cancer immune reaction do not mean good prognosis for oncologic patients.