Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response
Abstract
The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is sufficient to induce asthma or atopic dermatitis-like phenotypes when selectively overexpressed in transgenic mice, or when driven by topical application of vitamin D3 or low-calcemic analogues. Although T and B cells have been reported to be dispensable for the TSLP-induced inflammation in these models, little is known about the downstream pathways or additional cell types involved in the inflammatory response driven by TSLP. To characterize the downstream effects of TSLP in vivo, we examined the effects of exogenous administration of TSLP protein to wild-type and genetically deficient mice. TSLP induced a systemic Th2 inflammatory response characterized by increased circulating IgE and IgG1 as well as increased draining lymph node size and cellularity, Th2 cytokine production in draining lymph node cultures, inflammatory cell infiltrates, epithelial hyperplasia, subcuticular fibrosis, and up-regulated Th2 cytokine and chemokine messages in the skin. Responses to TSLP in various genetically deficient mice demonstrated T cells and eosinophils were required, whereas mast cells and TNF-α were dispensable. TSLP-induced responses were significantly, but not completely reduced in IL-4- and IL-13-deficient mice. These results shed light on the pathways and cell types involved in TSLP-induced inflammation.
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Mice deficient in IL-13, IL-4R, or IL-13Rβ1, and animals treated with neutralizing antibodies to IL-13 or IL-4R, display reduced fibrosis following many different types of tissue injury.
“IL-13, IL-4R, and IL-13Rβ1-deficient mice as well as animals treated with neutralizing antibodies to IL-13 or IL-4R display reduced fibrosis following many different types of tissue injury136–140”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [140]
Type 2 cytokine signaling has a critical role in the progression of fibrosis.
“confirming a critical role for type 2 cytokine signaling in the progression of fibrosis”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [140]
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Self-citation
- Authors
- Jessup, H. K., Brewer, A. W., Omori, M., Rickel, E. A., Budelsky, A. L., Yoon, B.-R. P., Ziegler, S. F., & Comeau, M. R.
- Affiliations
- Amgen (United States) (US)
- MedImmune , Gathersburg, MD 20878
- Laboratory for Immune Regulation, Research Center for Allergy and Immunology , Yokohama, Kanagawa,
- Virginia Mason Medical Center (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09
- Volume
- 181
- Issue
- 6
- Pages
- 4311-4319
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2117400018
- Cited by
- 110
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 15 · 2012: 13
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar056113-05)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR056113)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- thymic stromal lymphopoietin, intradermal administration, type 2 inflammation, T cells, eosinophils, IL-4, IL-13, mast cells, TNF-α, IgE, IgG1, draining lymph nodes, epithelial hyperplasia, skin inflammation, asthma, atopic dermatitis, epithelial-derived cytokines
- MeSH terms
- Thymic Stromal Lymphopoietin, Animals, Cells, Cultured, Eosinophils, Female, Immunoglobulin E, Injections, Intradermal, Male, Mast Cells, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Skin, Thymus Gland, Signal Transduction, Cytokines, Stromal Cells, Immunoglobulin Class Switching, Mice, Knockout, Th2 Cells, Inflammation Mediators, Mice
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