Interleukin-33: A Key Player in Immune Response and Tissue Homeostasis

Molecular Structure and Expression

Interleukin-33 (IL-33) is a part of the IL-1, also known as nuclear factor, present in high endothelial venules (NF-HEV). The human gene, for IL-33 can be found on chromosome 9, at position 24. Makes a protein of 30kDa with a total of 270 amino acids forming it. When you look at its structure IL-33 has a nuclear localization region, an area that can bind to chromatin, an end part resembling the IL-1 and a cytokine domain that binds to receptors.

IL-33 is always present, in cells within the body’s tissues like skin cells and gut cells well as in fibroblasts and endothelial cells. It plays an essential role, in keeping the tissues healthy and responding to external factors.

Signalling Pathway and Receptor Interactions

The impacts of IL–33, in biology mainly occur when it binds to the ST2 receptor (IL-1RL1) which pairs up with IL-1RAcp (IL-1 receptor accessory protein) to create a duo. This connection sets off a series of signals involving:

• Myd88 recruitment
• The triggering of IRAK1/4 kinase
• Signalling pathway involving TRAF6 (TNFR associated factor)
• The movement of NF kappa B, into the cell nucleus
• Activation of MAP kinases is triggered

Physiological Functions and Immune Regulation

When IL-33 Is discharged from dead cells it acts as an alarm signal or a molecule indicative of damage (known as DAMP). Its main biological functions consist of the following:

• Starting and enhancing type 2 immune responses.
• Encouraging the healing and renewal of tissues.
• Preserving the integrity of the epithelial barrier
• Managing the balance, in tissue to maintain equilibrium (homeostasis).
• Regulation of learned reactions (adaptive immune response)

IL-33 plays a role, in coordinating responses to combat parasitic infections and is essential for mucosal immunity functions as well. Additionally, it supports the regulation of Treg cells in tissue indicating its relevance, in maintaining metabolic balance.

Pathological Implications and Therapeutic Potential

IL-33 signalling dysfunction has been linked to a range of health issues.

Allergic Disorders

1. Asthma
2. Atopic dermatitis
3. Allergic rhinitis

Inflammatory Diseases

1. Inflammatory bowel disease
2. Rheumatoid arthritis
3. Psoriasis

Other Conditions

1. Cardiovascular diseases
2. Cancer progression
3. Fibrotic disorders

Targeting the IL-33/ST2 axis, for therapy shows promise in treating allergic conditions with various methods currently being explored for this purpose.

Neutralizing antibodies against IL-33 or ST2

Soluble ST2 receptor variants

Small molecule inhibitors of IL-33 signalling

Trials conducted on this pathway have demonstrated encouraging outcomes in the treatment of asthma and atopic dermatitis; however, additional research is necessary to grasp the therapeutic possibilities and potential adverse effects of IL-33 pathway adjustments.

Suitable ELISA Kits

• IL-33 ELISA Kit
• Interleukin-33 ELISA Kit