A Novel Inhibitory Receptor (ILT3) Expressed on Monocytes, Macrophages, and Dendritic Cells Involved in Antigen Processing

Cella, Marina; Döhring, Christian; Samaridis, Jacqueline; Dessing, Mark C.; Brockhaus, Manfred; Lanzavecchia, Antonio; Colonna, Marco

doi:10.1084/jem.185.10.1743

Cited by 390 publications

(328 citation statements)

References 68 publications

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“…LILRB4 encodes for a receptor protein expressed by dendritic cells, monocytes, macrophages and endothelial cells that on binding of MHC class I molecules triggers T-cell inhibition. 27,28 This effect of suppressing inflammation has been shown in vivo in a mouse model. 29 In humans an inverse correlation between high expression of LILRB4 in patients that underwent organ transplant and development of chronic rejection has been reported, 30 which supports the anti-inflammatory effect of LILRB4.…”

Section: Discussionmentioning

confidence: 88%

New genetic associations detected in a host response study to hepatitis B vaccine

et al. 2010

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The immune response to hepatitis B vaccination differs greatly among individuals, with 5-10% of healthy people failing to produce protective levels of antibodies. Several factors have been implicated in determining this response, chiefly individual genetic variation and age. Aiming to identify genes involved in the response to hepatitis B vaccination, a two-stage investigation of 6091 single-nucleotide polymorphisms (SNPs) in 914 immune genes was performed in an Indonesian cohort of 981 individuals showing normal levels of anti-HBs versus 665 individuals displaying undetectable levels of anti-HBs 18 months after initial dose of the vaccine. Of 275 SNPs identified in the first stage (476 normal/372 nonresponders) with Po0.05, significant associations were replicated for 25 polymorphisms in 15 genes (503 normal/295 nonresponders). We validated previous findings (HLA-DRA, rs5000563, P-value combined ¼ 5.57 Â 10 À10 ; OR (95%CI) ¼ 0.61 (0.52-0.71)). In addition, we detected a new association outside of the human leukocyte antigen loci region that passed correction for multiple testing. This SNP is in the 3 0 downstream region of FOXP1, a transcription factor involved in B-cell development (P-value combined ¼ 9.2 Â 10 À6 ; OR (95%CI) ¼ 1.38 (1.2-1.6)).These findings might help to understand the biological reasons behind vaccine failure and other aspects of variation in the immune responses of healthy individuals.

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Section: Discussionmentioning

confidence: 88%

New genetic associations detected in a host response study to hepatitis B vaccine

et al. 2010

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“…A putative IREM-1 murine orthologue, CLM-1, has been recently shown to be also expressed mainly by myeloid cells [19]. A myeloidrestricted expression pattern has been observed for a number of immunoreceptors, such as TREM-1 [4] and PILRa [20], some ILT [21,22], and IREM-2, another member of the same family (Aguilar et al, submitted), indicating a possible role for these molecules in the regulation of the innate immune response. IREM-1 and IREM-2 are the only known members of the CMRF-35 family with a myeloid-restricted expression pattern; it is of note that UP-D1 and UP-D2 mAb do not cross-react with IREM-2.…”

Section: Discussionmentioning

confidence: 99%

“…PBMC were obtained from heparinized venous blood of healthy donors by Ficoll-Hypaque gradient centrifugation, washed with PBS, activated with 2 lg/ml PHA and further expanded in IL-2 (200 U/ml)-containing growing medium. Blood monocytes were isolated from PBMC by adhesion to plastic for 1 h at 37 C [21]; in some experiments, monocytes were cultured either alone or stimulated for 72 h with 1 lg/ml LPS (Sigma, St. Louis, MO) or 10 ng/ml IL-10 (PeproTech, UK). Immature dendritic cells were obtained by treatment of monocytes with 25 ng/ml IL-4 (R&D Systems, MN) + 100 ng/ml GM-CSF (Leucomax, Novartis) for 6 days and treated with LPS for an additional 48 h to achieve maturation.…”

Section: Cells and Antibodiesmentioning

confidence: 99%

IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

et al. 2004

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Using a three-hybrid strategy, we have identified a novel cell surface molecule which interacts with the Src homology 2 (SH2) domains of SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1), termed "immune receptor expressed on myeloid cells 1" (IREM-1). The full-length cDNA coding for a polypeptide of 290 amino acids presents an extracellular single V-type Ig domain, a transmembrane region and a cytoplasmic tail with five tyrosine residues, two of which are in the context of an immunoreceptor tyrosine-based inhibitory motif. Moreover, cDNA encoding for three other splicing forms of IREM-1, named IREM-1 splice variant (Sv)1, Sv2 and Sv3 were cloned by reverse transcription (RT)-PCR. The gene encoding for IREM-1 contains nine exons, is located on human chromosome 17 (17q25.1) and is homologous to previously identified molecules termed CMRF-35 and IRp60. RT-PCR, northern blot and FACS analysis with specific monoclonal antibodies indicated that IREM-1 is expressed on monocytes, granulocytes, and myeloid leukemia cell lines. Western blot analysis confirmed the recruitment of SHP-1 to IREM-1 and demonstrated that phosphotyrosine residue 205 is the main docking site for this interaction. Finally, crosslinking of IREM-1 results in the inhibition of FcRe-induced activation. Our results indicate that IREM-1 is a novel inhibitory receptor of the Ig superfamily in myeloid cells.

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“…El primer grupo incluye los receptores que contienen ITIM, tales como ILT2, ILT3, ILT4, ILT5 y LIR8. Estos receptores inhiben la activación celular por el reclutamiento de proteínas fosfatasas de tirosina SHP-1 (50,51). El segundo grupo se caracteriza por la presencia de una corta cola citoplásmica a la que le faltan motivos de reconocimiento para los mediadores de señalización y por la presencia de residuos básicos de arginina en la región hidrofóbica trasmembrana, tales como ILT1, ILT7, ILT8 y LIR6a.…”

Section: Aspectos Generalesunclassified

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Arboleda¹,

García²,

Álvarez³

2011

biomedica

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Las células dendríticas son las células presentadores de antígeno más potentes y, por lo tanto, son importantes en el desencadenamiento de la respuesta inmunitaria frente a aloantígenos; sin embargo, también juegan un papel fundamental en el mantenimiento de la tolerancia periférica. La tolerancia es potenciada por la expresión en estas células de los receptores inhibidores ILT3 e ILT4, los cuales, mediante el reclutamiento de fosfatasas de tirosinas a sus dominios ITIM, inhiben la activación de la célula presentadora de antígeno y conducen a una débil respuesta de la célula T. Estos receptores propician, además, una interacción bidireccional con células T supresoras, T reguladoras o ambas, generando una cascada inmunorreguladora específica de antígeno, en la cual la célula dendrítica se comporta como una célula "tolerogénica". En esta revisión analizamos la biología y el comportamiento de las células dendríticas tolerogénicas que expresan altos niveles de ILT3 e ILT4, así como algunos aspectos moleculares y genéticos de estos receptores y su importancia en la modulación de las respuestas inmunitarias específicas de aloantígeno frente a un trasplante.Palabras clave: trasplante, células dendríticas, tolerancia inmunológica, inmunomodulación, supervivencia. ILT3 + /ILT4 + tolerogenic dendritic cells and their influence on allograft survivalDendritic cells, the most powerful antigen-presenting cells, are important for triggering of the immune responses to allo-antigens. However, they also play a fundamental role in the peripheral tolerance maintenance. Tolerance is enhanced by the presence on the dendritic cell surface of the inhibitor receptors ILT3 and ILT4. They recruit protein tyrosine-phosphatases to their ITIM domains and inhibit antigen-presenting cell activation, leading T cell hypo-responsivensess. Moreover, these receptors favor a bidirectional interaction with T-suppressor and T-regulator cells, generating an antigen-specific immunoregulator cascade, in which the dendritic cell behaves as a tolerogenic cell. In the current review, analysis is centered on the biology and behavior of the tolerogenic dendritic cells that express high levels of ILT3 and ILT4. Some molecular and genetics aspects of these receptors are discussed as well as their importance in the modulation of the allo-specific antigen immune response to transplants.

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A Novel Inhibitory Receptor (ILT3) Expressed on Monocytes, Macrophages, and Dendritic Cells Involved in Antigen Processing

Cited by 390 publications

References 68 publications

New genetic associations detected in a host response study to hepatitis B vaccine

New genetic associations detected in a host response study to hepatitis B vaccine

IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

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