LAIR2 localizes specifically to sites of extravillous trophoblast invasion

Founds, Sandra A.; Fallert-Junecko, Beth; Reinhart, Todd A.; Conley, Yvette P.; Parks, W. Tony

doi:10.1016/j.placenta.2010.07.005

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…Protein expression of LAIR-2 by EVT was confirmed by histological staining of anchoring cytotrophoblast columns, in agreement with a recent study [54]. ELISA detected secreted LAIR-2 in trophoblast culture supernatants and urine of pregnant women.…”

Section: Discussionsupporting

confidence: 91%

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

et al. 2011

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We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray. Villous trophoblast (VT) is in contact with maternal blood and mediates nutrient exchange whereas extravillous trophoblast (EVT) invades the decidua and remodels uterine arteries. Using highly purified first trimester trophoblast we identified over 3000 transcripts that are differentially expressed. Many of these transcripts represent novel functions and pathways that show co-ordinated up-regulation in VT or EVT. In addition we identify new players in established functions such as migration, immune modulation and cytokine or angiogenic factor secretion by EVT. The transition from VT to EVT is also characterised by alterations in transcription factors such as STAT4 and IRF9, which may co-ordinate these changes. Transcripts encoding several members of the immunoglobulin-superfamily, which are normally expressed on leukocytes, were highly transcribed in EVT but not expressed as protein, indicating specific control of translation in EVT. Interactions of trophoblast with decidual leukocytes are involved in regulating EVT invasion. We show that decidual T-cells, macrophages and NK cells express the inhibitory collagen receptor LAIR-1 and that EVT secrete LAIR-2, which can block this interaction. This represents a new mechanism by which EVT can modulate leukocyte function in the decidua. Since LAIR-2 is detectable in the urine of pregnant, but not non-pregnant women, trophoblast-derived LAIR-2 may also have systemic effects during pregnancy.

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Section: Discussionsupporting

confidence: 91%

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

et al. 2011

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“…In contrast to sLAIR‐1, monomer LAIR‐2 is an efficient inhibitor of the LAIR‐1–collagen interaction and, thus, may prevent the binding of collagen to LAIR‐1 expressed on cells. Endogenous LAIR‐2 has been shown to bind the extracellular matrix of chorionic villi ex vivo (18), thus supporting this notion. LAIR‐2 is produced by T cells, which also express LAIR‐1.…”

Section: Discussionmentioning

confidence: 80%

Enhanced secretion of leukocyte-associated immunoglobulin-like receptor 2 (LAIR-2) and soluble LAIR-1 in rheumatoid arthritis: LAIR-2 is a more efficient antagonist of the LAIR-1-collagen inhibitory interaction than is soluble LAIR-1

Nordkamp¹,

Roon²,

Douwes³

et al. 2011

Arthritis & Rheumatism

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Objective. Human leukocyte-associated immunoglobulin-like receptor 1 (hLAIR-1) is an immune inhibitory receptor for collagen that is expressed on most immune cells. We previously showed that the LAIR-1-collagen interaction could be antagonized by the secreted homolog hLAIR-2, which can be detected in the synovial fluid of rheumatoid arthritis (RA) patients. In addition, the extracellular part of hLAIR-1 is a putative antagonist upon shedding from the cell membrane. The purpose of this study was to determine the relative roles of hLAIR-2 and soluble hLAIR-1 (shLAIR-1) in the regulation of the LAIR-1-collagen interaction.Methods. The ability of recombinant LAIR proteins to abrogate LAIR-1-collagen binding was tested by flow cytometry and adhesion assays. Collagen binding capacity was analyzed by surface plasmon resonance. Plasma, urine, and synovial fluid were screened for the presence of sLAIR-1 and LAIR-2 by enzyme-linked immunosorbent assay.Results. Recombinant LAIR-2 proteins abrogated the binding of collagen to LAIR-1 more efficiently than did recombinant sLAIR-1. Consistent with these findings, surface plasmon resonance analysis showed that LAIR-2 had a higher affinity for collagen than did LAIR-1. Activated CD4؉ T cells were the main producers of LAIR-2, whereas the source of sLAIR-1 remains elusive. Both soluble LAIR-1 and LAIR-2 could be detected in the plasma and urine of healthy control subjects and patients with RA. Urinary levels of both proteins were significantly increased in RA patients, and LAIR-2 levels in urine were significantly correlated with markers of inflammation. Conclusion. Our data suggest that LAIR-2 is a more potent antagonist of LAIR-1 function in vivo, while both sLAIR-1 and LAIR-2 are potential biomarkers that may be used to monitor urine samples for evidence of systemic inflammation.Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory immune receptor for collagens and is expressed on most immune cells (1-3). Upon triggering, LAIR-1 inhibits various cellular functions (2,4-8). Since receptor and ligand are widely expressed, the regulation of the interaction must be tightly controlled to allow for appropriate cellular activation. We and other investigators have previously shown that upon maturation or activation, LAIR-1 expression on neutrophils, T cells, and B cells decreases, providing a regulatory mechanism at the level of receptor expression (8-11).

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“…Among these collagen receptors only the integrin heterodimers α 1 β 1 and α 2 β 1 and soluble receptor LAIR-2 are known to be expressed by trophoblast [20–22] . LAIR-2 is exclusively expressed by invading trophoblast cells and is significantly down-regulated in chorionic villous samples from women who subsequently develop pre-eclampsia [23,24] . Integrins alpha 10 (α10) and alpha 11 (α11) and collagen receptors DDR-1 and DDR-2 that also bind to col-IV and fibril-forming collagens are linked with the progression of various tumours via mediating cell migration [25–28] .…”

Section: Introductionmentioning

confidence: 99%

Collagen type IV at the fetal–maternal interface

et al. 2015

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IntroductionExtracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear.MethodsImmunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry.ResultsCol-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined.DiscussionCol-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site.

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LAIR2 localizes specifically to sites of extravillous trophoblast invasion

Cited by 16 publications

References 26 publications

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

Enhanced secretion of leukocyte-associated immunoglobulin-like receptor 2 (LAIR-2) and soluble LAIR-1 in rheumatoid arthritis: LAIR-2 is a more efficient antagonist of the LAIR-1-collagen inhibitory interaction than is soluble LAIR-1

Collagen type IV at the fetal–maternal interface

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