Page 972 - Veterinary Immunology, 10th Edition

IL-33 is a member of the IL-1 family that is crucial for the induction
VetBooks.ir of type 2 immune responses (Fig. 29.12). It is found in many tissues

where it normally regulates DNA transcription. It is not secreted
like a conventional cytokine but functions as an alarmin when it

escapes from the nuclei of damaged, infected, or dying cells. Its
production is increased during inflammation. IL-33 acts on many
different targets including Th2 cells, ILC2 cells, NK cells, dendritic
cells, mast cells, eosinophils, basophils, B cells, and neurons. It is a

key inducer of the Th2 cytokines, IL-4, -5, and -13. (IL-33 together
with IL-25 and TSLP are all promoters of Th2 responses. IL-33 is the
most potent.) When released by damaged cells, IL-33 is cleaved by
inflammatory proteases to shorter peptides that activate group 2

ILCs and triggers them to produce IL-5 and IL-13, and so stimulates
eosinophil production. It initiates the Th2 polarizing functions of
DC2 dendritic cells.

FIG. 29.12 The biological properties of interleukin-33. IL-33 is
released by dying cells as well as epithelial cells in response to
PAMPs. It stimulates the production of inflammatory cytokines and

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