Chest
Translating Basic Research Into Clinical PracticeEpithelial-Derived Cytokines in Asthma
Section snippets
Epithelial-Derived IL-25
IL-25 is an epithelial-derived cytokine that is also known as IL-17E. It is a member of the IL-17 cytokine family and is expressed by airway epithelial cells, T-helper-2 polarized cells, activated mast cells, basophils, and eosinophils.7, 8 IL-25 is unique among the IL-17 family of cytokines, in that it can initiate eosinophilia and upregulate type 2 cytokine production.9 IL-25 is stored in, and released from, the extranuclear cellular compartment. It is constitutively expressed in epithelial
Epithelial-Derived IL-33
IL-33 is a member of the IL-1 cytokine family.20 Epithelial cells from tissues exposed to the external environment, such as eyes, skin, intestine, and airways, and lymphoid organs, keratinocytes, smooth muscle cells, and human endothelial cells produce IL-33.21, 22 Immune cells also express IL-33, including macrophages, DCs, mast cells, and monocytes, but at a 10-fold lower level than epithelial cells.23, 24 IL-33 is not expressed in CD45+ve hematopoietic cells under basal conditions, but it
Epithelial-Derived TSLP
TSLP is part of the IL-2 cytokine family, the gene for which is localized on chromosome 5q22.1, which is next to the atopic cytokine gene cluster, 5q31, which encodes IL-4, IL-5, IL-9, and IL-13. TSLP binds to a high-affinity receptor complex that consists of the thymic stromal lymphopoietin receptor (TSLPR) and an IL-7Rα subunit. The receptor is expressed on many cell types, which include myeloid DCs, CD4+ve and CD8+ve T cells, regulatory T cells, B cells, mast cells, NKT cells, monocytes,
Conclusions
There has been great progress in the study of the responses of the airway epithelium to allergens and infection. The airway epithelium constitutes the first physical, chemical, and immunologic barrier to inhaled agents. Epithelial cells express pattern recognition receptors, integrate information from many receptors simultaneously, and bridge the innate and adaptive immune system cells through the release of chemokines and cytokines.
Evidence is accumulating that epithelial-derived alarmins,
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: P. O. B. reports grants and personal fees from AstraZeneca, personal fees from Chiesi, grants from Novartis, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from MedImmune, personal fees from Merck, personal fees from Abbott, grants from Amgen, grants from Genentech, and grants from Axican outside the submitted work. None declared (P. D. M.).
Other contributions: We thank Mark
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