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6  structures 36  species 0  interactions 43  sequences 2  architectures

Family: TSLP (PF15216)

Summary: Thymic stromal lymphopoietin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Thymic stromal lymphopoietin". More...

Thymic stromal lymphopoietin Edit Wikipedia article

TSLP
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TSLP, thymic stromal lymphopoietin
External IDs MGI: 1855696 HomoloGene: 81957 GeneCards: TSLP
Gene location (Human)
Chromosome 5 (human)
Chr. Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for TSLP
Genomic location for TSLP
Band 5q22.1 Start 111,070,062 bp[1]
End 111,078,024 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_033035
NM_138551

NM_021367

RefSeq (protein)

NP_149024
NP_612561

NP_067342

Location (UCSC) Chr 5: 111.07 – 111.08 Mb Chr 5: 32.82 – 32.82 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

TSLP production has been observed in various species, including humans and mice. In humans TSLP is encoded by the TSLP gene.[5][6] Alternative splicing of this gene results in two transcript variants.[6]

Function

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.[7] TSLP has also been shown to activate the maturation of a specific subset of dendritic cells located within the epidermis, called Langerhans cells.[8] Within the thymus TSLP activation of both myeloid and plasmacytoid (CD123+) dendritic cells results in the production of regulatory T cells.[9][10]

Signalling

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.[11]

Disease

TSLP expression is linked to many disease states including asthma,[12] inflammatory arthritis,[13] atopic dermatitis,[8] eczema, eosinophilic esophagitis and other allergic states.[14][15] The factors inducing the activation of TSLP release are not clearly defined.

Asthma

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).[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

Atopic dermatitis

TSLP-activated Langerhans cells of the epidermis induce the production of pro-inflammatory cytokines like TNF-alpha by T cells potentially causing atopic dermatitis.[8] 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.[16]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145777 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024379 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ 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. 
  6. ^ a b "Entrez Gene: TSLP thymic stromal lymphopoietin". 
  7. ^ 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. 
  8. ^ 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. PMID 17320941. doi:10.1016/j.jaci.2007.01.003. 
  9. ^ 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. 
  10. ^ 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 3325785Freely accessible. PMID 20173030. doi:10.4049/jimmunol.0804106. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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 2700555Freely accessible. PMID 19557146. doi:10.1371/journal.pbio.1000067. Lay summary – BBC News. 

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Thymic stromal lymphopoietin Provide feedback

No Pfam abstract.

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].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan 4H_Cytokine (CL0053), which has the following description:

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 [2]. 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

Alignments

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(8)
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(141)
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(13)
RP55
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RP75
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(8)
Full
(43)
Representative proteomes UniProt
(64)
NCBI
(141)
Meta
(0)
RP15
(4)
RP35
(13)
RP55
(29)
RP75
(45)
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  Seed
(8)
Full
(43)
Representative proteomes UniProt
(64)
NCBI
(141)
Meta
(0)
RP15
(4)
RP35
(13)
RP55
(29)
RP75
(45)
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Trees

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Jackhmmer:Q969D9
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 31.3 31.0
Noise cut-off 22.4 20.2
Model length: 125
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

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Structures

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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