Cutting Edge: KIR2DL4 Transduces Signals into Human NK Cells through Association with the Fc Receptor γ Protein

Kikuchi-Maki, Akiko; Catina, Tracey L.; Campbell, Kerry S.

doi:10.4049/jimmunol.174.7.3859

Cited by 126 publications

(103 citation statements)

References 27 publications

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“…EAT is expressed in all peripheral macrophages and may be responsible for the activating phenotype of decidual macrophages. KIR2DL4 on decidual NK cells also encodes both an ITIM in its cytoplasmic region and an activating module, in this case an arginine residue in its transmembrane region that associates with the signaling module Fc RI␥ (40). Further studies of control of the signaling potential of these two types of decidual cells are needed.…”

Section: Discussionmentioning

confidence: 99%

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Houser²,

Nicotra³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

150

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Human decidual CD14 ؉ macrophages and CD56 ؉ NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class Ib protein that is expressed on extravillous trophoblasts), LILRB1 on CD14 ؉ macrophages and KIR2DL4 on CD56 ؉ NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNF␣ detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.IL-6 ͉ IL-8 ͉ pregnancy ͉ trophoblast ͉ VEGF

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Section: Discussionmentioning

confidence: 99%

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Houser²,

Nicotra³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

150

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“…36 It has a charged arginine residue in its transmembrane domain that allows it to pair with FceRIc to signal for weak cytotoxicity and cytokine secretion at the cell surface. 37 The non-classical MHC-I molecule HLA-G is the ligand for KIR2DL4. The soluble form of HLA-G is likely to be the natural ligand as it accumulates into endosomes containing KIR2DL4.…”

Section: Kir2dl4-hla-g Interactions and Endosomal Signalingmentioning

confidence: 99%

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

Rajagopalan

2014

Cell Mol Immunol

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The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer (NK) cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex (MHC) molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor (KIR) family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen (HLA)-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype (SASP) in vascular remodeling will be discussed in the context of reproduction.

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“…14 KIR2DL5 displays a variegated distribution on the surface of CD56 dim NK cells, whereas the surface expression of KIR2DL4 appears to be restricted to the minority subset of KIR neg CD56 bright NK cells. 8,15 Although KIR2DL4 has been implicated in both inhibitory and activating functions, 6,[16][17][18] KIR2DL5 appears to be solely an inhibitory receptor. 7 Multiple sequences for both KIR2DL5A and KIR2DL5B loci have been characterized from individuals of different ethnic origins.…”

Section: Introductionmentioning

confidence: 99%

KIR2DL5 alleles mark certain combination of activating KIR genes

Sharma

Spellman

et al. 2008

Genes Immun

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Killer cell Ig-like receptors (KIR) control the immune response of NK cells and some T cells to infections and tumors. KIR genes evolve rapidly and are variable between individuals in their number, type and sequence. Here, we determined the nature of KIR2DL5 gene polymorphism in four ethnic groups using direct DNA sequencing method. Nine new sequences were discovered. Within the panel of 248 KIR2DL5-positive individuals, 14 KIR2DL5-sequences differing in coding regions were observed. They differed at only seven amino acid positions, and such limited polymorphism is consistent with its conserved nature throughout the hominoid lineage. Ethnic deviation was seen in the distribution of KIR2DL5A, KIR2DL5B and their alleles. African Americans had more KIR2DL5 alleles than other populations indicating that more polymorphisms are yet to be discovered in Africans. Linkage between KIR2DL5-alleles and certain activating-KIR genes were observed, but frequency of these linked clusters differed substantially between populations. Consequently, KIR2DL5 alleles can be used as markers to predict the activating-KIR gene content. Typing system distinguishing A*001 and B*002 alleles can serve as a powerful screening test to assess the content of most variable activating-KIR genes that have been implicated in human disease and in the outcome of hematopoietic stem cell transplantation.

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Cutting Edge: KIR2DL4 Transduces Signals into Human NK Cells through Association with the Fc Receptor γ Protein

Cited by 126 publications

References 27 publications

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

KIR2DL5 alleles mark certain combination of activating KIR genes

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