Modulation of the inhibitory receptor leukocyte Ig-like receptor 1 on human natural killer cells

Li, Nicholas L.; Davidson, Courtney; Humar, Atul; Burshtyn, Deborah N.

doi:10.3389/fimmu.2011.00046

Cited by 8 publications

(9 citation statements)

References 56 publications

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“…In the same line, most LILRB1 + cells were predominantly found among the CD27‐negative cell population , corresponding to late NK differentiation stages . Recent studies indicate that LILRB1 expression may be also upregulated in NK cells upon in vitro exposure to cytokines . Hence, the marked increase of LILRB1 + NK populations in symptomatic congenital HCMV infection likely reflects the accumulation of cells activated/differentiated under the pressure of the pathogen.…”

Section: Discussionmentioning

confidence: 87%

Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Noyola¹,

Fortuny

Muntasell

et al. 2012

Eur J Immunol

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Human cytomegalovirus (HCMV) has been reported to reshape the NK-cell receptor (NKR) distribution, promoting an expansion of CD94/NKG2C + NK and T cells. The role of NK cells in congenital HCMV infection is ill-defined. Here we studied the expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the NKG2C gene deletion in children with past congenital infection, both symptomatic (n = 15) and asymptomatic (n = 11), including as controls children with postnatal infection (n = 11) and noninfected (n = 20). The expansion of NKG2C + NK cells in HCMV-infected individuals appeared particularly marked and was associated with an increased number of LILRB1 + NK cells in cases with symptomatic congenital infection. Increased numbers of NKG2C + , NKG2A + , and CD161 + T cells were also associated to HCMV infection. The NKG2C deletion frequency was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous NKG2C +/+ genotype appeared associated with increased absolute numbers of NKG2C + NK cells. Moreover, HCMV-infected NKG2C +/+ children displayed higher absolute numbers of NKG2A + and total NK cells than NKG2C +/− individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK-cell compartment in children, revealing a modulatory influence of NKG2C copy number. Eur. J. Immunol. 2012. 42: 3256-3266 Immunity to infection 3257 lifelong latent state, occasionally undergoing reactivation, but may have a pathogenic role in immunodeficient and immunosuppressed patients [1][2][3]. Moreover, HCMV has been associated with atherosclerosis, lymphoproliferative disorders, and glioblastoma, as well as with an accelerated immunosenescence and a shorter lifespan [4][5][6][7]. Vertical transmission of HCMV during pregnancy is considered the most common cause of congenital infection worldwide, affecting ∼0.2-2% of infants and potentially causing fetal lesions [8][9][10]. Though most infected newborns are asymptomatic, ∼10% display a variety of clinical disorders [8,11] potentially leading to important sequelae such as mental retardation and deafness. The type of maternal infection (i.e., primary versus reactivation/reinfection) conditions the risk of congenital infection and the pregnancy stage at which transmission occurs is related to clinical severity [12][13][14][15][16]. Maternal antibodies with neutralizing activity are transferred to the fetus predominantly during the third trimester of gestation and may prevent congenital CMV disease [17]. Among other factors, fetal immune immaturity may determine the outcome of congenital infection [18,19]. An effective defense against HCMV requires the participation of T and NK cells, and the virus has developed different immune evasion strategies [20]. Patients with congenital HCMV infection have been shown to display mature CD8 + T-cell responses [21,22], and an expansion and differentiation of a specific TcR γδ + cell subset has been recently reported [23]. In contrast, information on the role of...

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Section: Discussionmentioning

confidence: 87%

Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Noyola¹,

Fortuny

Muntasell

et al. 2012

Eur J Immunol

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“…19 Furthermore, the frequency of LILRB1-positive NK cells in an individual fluctuates over time. 20 Moreover, the cell surface expression intensity differs among LILRB1 haplotypes. 21 A low-expressing LILRB1 haplotype is significantly associated with rheumatoid arthritis (RA) susceptibility in HLA-DRB1 shared epitope negative subjects, possibly because of insufficient inhibitory signaling in leukocytes.…”

Section: Introductionmentioning

confidence: 99%

Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations

Hirayasu

Arase

2015

J Hum Genet

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Human leukocyte immunoglobulin-like receptors (LILR) are a family of 11 functional genes encoding five activating (LILRA1, 2, 4-6), five inhibitory (LILRB1-5) and one soluble (LILRA3) form. The number of LILR genes is conserved among individuals, except for LILRA3 and LILRA6, which exhibit copy-number variations. The LILR genes are rapidly evolving and showing large interspecies differences, making it difficult to analyze the functions of LILR using an animal model. LILRs are expressed on various cells such as lymphoid and myeloid cells and the expression patterns are different from gene to gene. The LILR gene expression and polymorphisms have been reported to be associated with autoimmune and infectious diseases such as rheumatoid arthritis and cytomegalovirus infection. Although human leukocyte antigen (HLA) class I is a well-characterized ligand for some LILRs, non-HLA ligands have been increasingly identified in recent years. LILRs have diverse functions, including the regulation of inflammation, immune tolerance, cell differentiation and nervous system plasticity. This review focuses on the genetic and functional diversity of the LILR family.

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“…LILRB1 expression may be upregulated by several mechanisms during CMV infection. For example, purified NK cells cultured in the presence of IL‐15 and IL‐2 show an increase in LILRB1 expression . CMV produces a persistent infection that is associated with chronic activation of the immune system .…”

Section: Discussionmentioning

confidence: 99%

Effect of cytomegalovirus infection and leukocyte immunoglobulin like receptor B1 polymorphisms on receptor expression in peripheral blood mononuclear cells

Cadena‐Mota

Monsiváis‐Urenda

Salgado‐Bustamante

et al. 2018

Microbiology and Immunology

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Leukocyte immunoglobulin like receptor B1 (LILRB1) plays a significant role in a number of infectious, autoimmune, cardiovascular, and oncologic disorders. LILRB1 expression varies between individuals and may be associated with polymorphisms on the regulatory region of the LILRB1 gene, as well as to previous cytomegalovirus infection. In this study, the contribution of these two factors to LILRB1 expression in peripheral blood mononuclear cells of healthy young adults was analyzed. LILRB1 expression in NK cells, T cells, B cells and monocytes was significantly stronger in individuals who had had cytomegalovirus infection than in those who had not (P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Overall, no differences in LILRB1 expression were observed between individuals with and without GAA haplotypes of the LILRB1 regulatory region. However, when analyzed according to cytomegalovirus infection status, significant differences in LILRB1+ NK cells were observed. A higher proportion of LILRB1+ cells was found in GAA+ than in GAA− individuals who had not been infected (P < 0.01), whereas GAA− individuals had a larger proportion of LILRB1+ cells than GAA+ individuals who were cytomegalovirus positive (P < 0.01). In conclusion, cytomegalovirus infection has a major effect on LILRB1 expression in NK and other mononuclear cells and polymorphisms in the LILRB1 regulatory region appear to have a modulatory influence over this effect.

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Modulation of the inhibitory receptor leukocyte Ig-like receptor 1 on human natural killer cells

Cited by 8 publications

References 56 publications

Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations

Effect of cytomegalovirus infection and leukocyte immunoglobulin like receptor B1 polymorphisms on receptor expression in peripheral blood mononuclear cells

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