Thymic stromal lymphopoietin

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Thymic stromal lymphopoietin
Identifiers
Symbol TSLP
External IDs OMIM607003 MGI1855696 HomoloGene81957 GeneCards: TSLP Gene
Orthologs
Species Human Mouse
Entrez 85480 53603
Ensembl ENSG00000145777 ENSMUSG00000024379
UniProt Q969D9 Q9JIE6
RefSeq (mRNA) NM_033035 NM_021367
RefSeq (protein) NP_149024 NP_067342
Location (UCSC) Chr 5:
110.41 – 110.41 Mb
Chr 18:
32.82 – 32.82 Mb
PubMed search [1] [2]

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.[citation needed] These cells are located in regions where TSLP activity is required.

Gene ontology[edit]

TSLP production has been observed in various species, including humans and mice. In humans TSLP is encoded by the TSLP gene.[1][2] Alternative splicing of this gene results in two transcript variants.[2]

Function[edit]

It mainly impacts myeloid cells and induces the release of T cell-attracting chemokines from monocytes[citation needed] and enhances the maturation of myeloid (CD11c+) dendritic cells.[3] TSLP has also been shown to activate the maturation of a specific subset of dendritic cells located within the epidermis, called Langerhans cells.[4] Within the thymus TSLP activation of both myeloid and plasmacytoid (CD123+) dendritic cells results in the production of regulatory T cells.[5][6]

Signalling[edit]

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.[7]

Disease[edit]

TSLP expression is linked to many disease states including asthma,[8] inflammatory arthritis,[9] atopic dermatitis,[4] and eczema and other allergic states.[10][11] The factors inducing the activation of TSLP release are not clearly defined.

Asthma[edit]

Expression of TSLP is enhanced under asthma-like conditions (aka Airway HyperResponsiveness or AHR model in the mouse), conditioning APCs in order to orientate the differentiation of T cells coming into the lungs towards a TH2 profile (T helper 2 pathway).[citation needed] The TH2 cells then release factors promoting an inflammatory reaction following the repeated contact with a specific antigen in the airways[citation needed].

Inflammatory arthritis[edit]

Atopic dermatitis[edit]

TSLP-activated Langerhan cells of the epidermis induce the production of pro-inflammatory cytokines like TNF-alpha by T cells potentially causing atopic dermatitis.[4] 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.[12]

References[edit]

  1. ^ 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. doi:10.1038/sj.leu.2402175. PMID 11480573. 
  2. ^ a b "Entrez Gene: TSLP thymic stromal lymphopoietin". 
  3. ^ 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. 
  4. ^ a b c 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. doi:10.1016/j.jaci.2007.01.003. PMID 17320941. 
  5. ^ 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. doi:10.1038/nature03886. PMID 16121185. 
  6. ^ 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. doi:10.4049/jimmunol.0804106. PMC 3325785. PMID 20173030. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. doi:10.1016/j.bbrc.2007.03.081. PMID 17416344. 
  10. ^ 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. doi:10.1007/s00281-003-0152-0. PMID 14999427. 
  11. ^ 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. doi:10.1038/ni805. PMID 12055625. 
  12. ^ 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. doi:10.1371/journal.pbio.1000067. PMC 2700555. PMID 19557146. Lay summaryBBC News. 

Further reading[edit]