Interleukin-33 in Asthma: How Big of a Role Does It Play?
- First Online:
In complex disorders such as asthma and allergic disease, the goal for developing disease-modifying biotherapeutics is to find a target that is a central instigator of immunologic activity. Interleukin (IL)-33 seems to be such a molecule, as it is one of the earliest-released signaling molecules following epithelial damage and can orchestrate the recruitment and activation of the cells responsible for disease. Unregulated IL-33 activity leads to activation of T-helper type 2 cells, mast cells, dendritic cells, eosinophils, and basophils, ultimately leading to increased expression of cytokines and chemokines that define the disease. As such, IL-33 is an attractive candidate for therapeutic intervention with the goal of ameliorating disease. This review focuses on the role of IL-33 in promoting and maintaining the asthma phenotype.
KeywordsAsthma Interleukin-33 ST2 Interleukin-1 family
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 6.•• Luthi AU, Cullen SP, McNeela EA, et al.: Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 2009, 31:84–98, It was believed that IL-33 was activated by caspases, similar to other members of the IL-1 family; however, this article demonstrated that IL-33 was active in the uncleaved form and was only released following necrosis caused by cell damage.CrossRefPubMedGoogle Scholar
- 10.Dunne A, O’Neill LA: The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003, 2003:re3.Google Scholar
- 13.Pecaric-Petkovic T, Didichenko SA, Kaempfer S, et al.: Human basophils and eosinophils are the direct target leukocytes of the novel IL-1-family member IL-33. Blood 2009, 113:1396–1397.Google Scholar
- 24.• Rank MA, Kobayahi T, Kozaki H, et al.: IL-33-activated dendritic cells induce an atypical TH2-type response. J Allergy Clin Immunol 2009, 123:1047–1054, This article demonstrated that DCs respond to IL-33 through the ST2 receptor. When these stimulated DCs were cultured with naïve T cells, they were able to induce expression of IL-5 and IL-13.CrossRefPubMedGoogle Scholar
- 33.• Kearley J, Buckland KF, Mathie SA, Lloyd CM: Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway. Am J Respir Crit Care Med 2009, 179:772–781, Using a murine model of allergic disease, these authors demonstrated that blockade of ST2 prevented development of airway hyperreactivity and an increase of Th2 cells into the lung. IL-33 levels were increased during active lung inflammation.CrossRefPubMedGoogle Scholar