Summary: Thymic stromal lymphopoietin
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Thymic stromal lymphopoietin Edit Wikipedia article
|, thymic stromal lymphopoietin|
Thymic stromal lymphopoietin (TSLP) is a protein belonging to the cytokine family. It is known to play an important role in the maturation of T cell populations through activation of antigen presenting cells.
TSLP is produced mainly by non-hematopoietic cells such as fibroblasts, epithelial cells and different types of stromal or stromal-like cells. These cells are located in regions where TSLP activity is required.
TSLP production has been observed in various species, including humans and mice. In humans TSLP is encoded by the TSLP gene. Alternative splicing of this gene results in two transcript variants.
It mainly impacts myeloid cells and induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of myeloid (CD11c+) dendritic cells. TSLP has also been shown to activate the maturation of a specific subset of dendritic cells located within the epidermis, called Langerhans cells. Within the thymus TSLP activation of both myeloid and plasmacytoid (CD123+) dendritic cells results in the production of regulatory T cells.
TSLP signals through a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor CRLF2 and the IL-7R alpha chain. After binding STAT5 phosphorylation is induced resulting in the expression of upstream transcription factors.
TSLP expression is linked to many disease states including asthma, inflammatory arthritis, atopic dermatitis, eczema, eosinophilic esophagitis and other allergic states. The factors inducing the activation of TSLP release are not clearly defined.
Expression of TSLP is enhanced under asthma-like conditions (aka Airway HyperResponsiveness or AHR model in the mouse), conditioning APCs in order to orient the differentiation of T cells coming into the lungs towards a TH2 profile (T helper 2 pathway). The TH2 cells then release factors promoting an inflammatory reaction following the repeated contact with a specific antigen in the airways.
TSLP-activated Langerhans cells of the epidermis induce the production of pro-inflammatory cytokines like TNF-alpha by T cells potentially causing atopic dermatitis. It is thought that understanding the mechanism of TSLP production and those potential substances that block the production, one may be able to prevent or treat conditions of asthma and/or eczema.
- GRCh38: Ensembl release 89: ENSG00000145777 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000024379 - Ensembl, May 2017
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- Quentmeier H, Drexler HG, Fleckenstein D, Zaborski M, Armstrong A, Sims JE, Lyman SD (Aug 2001). "Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation". Leukemia. 15 (8): 1286–92. PMID 11480573. doi:10.1038/sj.leu.2402175.
- "Entrez Gene: TSLP thymic stromal lymphopoietin".
- Reche PA, Soumelis V, Gorman DM, et al. (July 2001). "Human thymic stromal lymphopoietin preferentially stimulates myeloid cells". J. Immunol. 167 (1): 336–43. PMID 11418668. doi:10.4049/jimmunol.167.1.336.
- Ebner S, Nguyen VA, Forstner M, Wang YH, Wolfram D, Liu YJ, Romani N (April 2007). "Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells". J. Allergy Clin. Immunol. 119 (4): 982–90. PMID 17320941. doi:10.1016/j.jaci.2007.01.003.
- Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ (August 2005). "Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus". Nature. 436 (7054): 1181–5. PMID 16121185. doi:10.1038/nature03886.
- Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL, Roman E, Arima K, Wang YH, Voo KS, Cao W, Liu YJ (March 2010). "Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus". J. Immunol. 184 (6): 2999–3007. PMC . PMID 20173030. doi:10.4049/jimmunol.0804106.
- Isaksen DE, Baumann H, Trobridge PA, Farr AG, Levin SD, Ziegler SF (December 1999). "Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction". J. Immunol. 163 (11): 5971–7. PMID 10570284.
- Ying S, O'Connor B, Ratoff J, Meng Q, Mallett K, Cousins D, Robinson D, Zhang G, Zhao J, Lee TH, Corrigan C (June 2005). "Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity". J. Immunol. 174 (12): 8183–90. PMID 15944327. doi:10.4049/jimmunol.174.12.8183.
- Koyama K, Ozawa T, Hatsushika K, Ando T, Takano S, Wako M, Suenaga F, Ohnuma Y, Ohba T, Katoh R, Sugiyama H, Hamada Y, Ogawa H, Okumura K, Nakao A (May 2007). "A possible role for TSLP in inflammatory arthritis". Biochem. Biophys. Res. Commun. 357 (1): 99–104. PMID 17416344. doi:10.1016/j.bbrc.2007.03.081.
- Soumelis V, Liu YJ (February 2004). "Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation". Springer Semin. Immunopathol. 25 (3-4): 325–33. PMID 14999427. doi:10.1007/s00281-003-0152-0.
- Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K, Gorman D, Zurawski S, Abrams J, Menon S, McClanahan T, de Waal-Malefyt Rd R, Bazan F, Kastelein RA, Liu YJ (July 2002). "Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP". Nat. Immunol. 3 (7): 673–80. PMID 12055625. doi:10.1038/ni805.
- Demehri S, Morimoto M, Holtzman MJ, Kopan R (May 2009). "Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma". PLoS Biol. 7 (5): e1000067. PMC . PMID 19557146. doi:10.1371/journal.pbio.1000067. Lay summary – BBC News.
- Ziegler SF, Liu YJ (2006). "Thymic stromal lymphopoietin in normal and pathogenic T cell development and function.". Nat. Immunol. 7 (7): 709–14. PMID 16785889. doi:10.1038/ni1360.
- Liu YJ (2007). "Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation.". J. Allergy Clin. Immunol. 120 (2): 238–44; quiz 245–6. PMID 17666213. doi:10.1016/j.jaci.2007.06.004.
- Gilliet M, Soumelis V, Watanabe N, et al. (2003). "Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.". J. Exp. Med. 197 (8): 1059–63. PMC . PMID 12707303. doi:10.1084/jem.20030240.
- Watanabe N, Hanabuchi S, Marloie-Provost MA, et al. (2005). "Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential.". Blood. 105 (12): 4749–51. PMID 15741223. doi:10.1182/blood-2004-09-3622.
- Lee HC, Ziegler SF (2007). "Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB.". Proc. Natl. Acad. Sci. U.S.A. 104 (3): 914–9. PMC . PMID 17213320. doi:10.1073/pnas.0607305104.
- Zhang K, Shan L, Rahman MS, et al. (2007). "Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease.". Am. J. Physiol. Lung Cell Mol. Physiol. 293 (2): L375–82. PMID 17513456. doi:10.1152/ajplung.00045.2007.
- Rochman I, Watanabe N, Arima K, et al. (2007). "Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells.". J. Immunol. 178 (11): 6720–4. PMID 17513717. doi:10.4049/jimmunol.178.11.6720.
- Wang YH, Angkasekwinai P, Lu N, et al. (2007). "IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.". J. Exp. Med. 204 (8): 1837–47. PMC . PMID 17635955. doi:10.1084/jem.20070406.
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This tab holds annotation information from the InterPro database.
InterPro entry IPR029189
Thymic stromal lymphopoietin (TSLP) is a cytokine that functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells [PUBMED:11418668]. TSLP has proliferative effects on the myeloid cell line [PUBMED:11480573] and may initiate asthma or atopic dermatitis responses by directly activating mast cells [PUBMED:17242164].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||cytokine activity (GO:0005125)|
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Cytokines are regulatory peptides that can be produced by various cells for communicating and orchestrating the large multicellular system. Cytokines are key mediators of hematopoiesis, immunity, allergy, inflammation, tissue remodeling, angiogenesis, and embryonic development . This superfamily includes both the long and short chain helical cytokines.
The clan contains the following 29 members:CNTF CSF-1 EPO_TPO Flt3_lig GCSF GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL15 IL2 IL22 IL23 IL28A IL3 IL34 IL4 IL5 IL6 IL7 Interferon Leptin LIF_OSM PRF SCF TSLP
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|Author:||Eberhardt R , Coggill P , Hetherington K|
|Number in seed:||8|
|Number in full:||43|
|Average length of the domain:||99.00 aa|
|Average identity of full alignment:||46 %|
|Average coverage of the sequence by the domain:||72.77 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TSLP domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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