The role of HLA-G in immunity and hematopoiesis

Carosella, Edgardo D.; Gregori, Silvia; Rouas‐Freiss, Nathalie; LeMaoult, Joël; Menier, Catherine; Favier, Benoît

doi:10.1007/s00018-010-0579-0

Cited by 57 publications

(43 citation statements)

References 171 publications

(232 reference statements)

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“…The HLA-G molecule is distinguished from the classical HLA class I molecules by (i) relatively low allelic polymorphism, (ii) a unique mRNA transcript leading to seven isoforms, (iii) a highly restricted tissue distribution [3]. The HLA-G1 isoform has a similar structure to that of the classical HLA class I molecules and differs only by a short intracellular tail composed of six amino acids compared with the 30 amino acids usually found in classical HLA class I molecules.…”

Section: Introductionmentioning

confidence: 99%

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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HLA-G is a non-classical HLA class I molecule with tolerogenic properties and restricted tissue distribution. The expression of HLA-G can be induced by tumors thus providing an efficient way to escape the anti-tumoral immune response. Although lipid rafts regulate diverse immunological mechanisms their relationship with HLA-G remains controversial. Our results show that HLA-G-mediated inhibition of both the interaction between NK and tumor cells, and of intracellular calcium flux in NK cells conjugated to their target cells were independent of lipid raft integrity. In addition, cytotoxicity assays indicated that HLA-G continued to efficiently inhibit NK-cell cytolytic function in several different tumor cells independently of lipid raft integrity. Confocal microscopy with 3D reconstruction combined with biochemical analysis showed that HLA-G was mainly localized outside the lipid rafts of tumor cells after cross-linking with specific antibody and remained excluded from lipid rafts during interaction with the ILT2 inhibitory receptor of NK cells. This study indicates that the inhibitory function of HLA-G is uncoupled from lipid raft organization, further distinguishing HLA-G from classical HLA molecules and providing novel information in the understanding of tumor immune escape mechanism mediated through HLA-G.

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Section: Introductionmentioning

confidence: 99%

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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“…Once recruited, these phosphatases can in turn deactivate activatory cascades. The interaction of ILT4 with HLA-G has been shown to inhibit the differentiation of monocytes into dendritic cells, suggesting a role of this receptor in the attenuation of inflammatory responses (9,10).…”

mentioning

confidence: 99%

Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions

Baudhuin

Migraine

Faivre

et al. 2013

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

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Neutrophils play a major role in inflammatory responses and immune defense against pathogens. Even though expression of inhibitory receptors has been reported on neutrophils, their role remains poorly defined. Here we show that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into "neutrophil-like" cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. ILT4 engagement also impaired reactive oxygen species production induced through CD32a and both receptors were found colocalized into neutrophil lipid rafts. Moreover, neutrophil degranulation induced through inflammatory stimuli increased ILT4 expression as a result of the rapid translocation of an intracellular pool to the cell surface. Consequently to this ILT4 upregulation, the human leukocyte antigen G-mediated inhibition of neutrophil phagocytic function was enhanced. Finally, we found that ILT4 up-regulation induced on healthy donor neutrophils following stimulation was impaired in presence of plasma from patients with sepsis. Similarly, ILT4 up-regulation was inhibited in neutrophils from septic patients. Altogether, our results reveal a unique mechanism of regulation of neutrophil functions through ILT4 and its exocytosis that may have implications in inflammatory disorders.granulocytes |

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“…As a consequence, HLA-G could directly inhibit the functions of NK cells, CTLs, B cells, neutrophils, DCs and MDSCs [31]. HLA-G has also indirect immune-regulatory activities by inducing tolerogenic cells including HLA-G-expressing APC, mesenchymal stem cells (MSCs), T regulatory (Treg) cells, CD4 low and CD8 low suppressor T cells, T regulatory type 1 (Tr1) cells, NK cells, and DC-10 cells [32,33]. Thus, HLA-G renders multiple effects in the suppression of immune responses.…”

Section: Discussionmentioning

confidence: 99%

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

Lu¹,

Li²,

Lin³

et al. 2017

J Antivir Antiretrovir

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Both human leukocyte antigen-G (HLA-G) and myeloid-derived suppressor cells (MDSCs) was associated with the pathogenesis of infectious diseases. Whether peripheral MDSCs express HLA-G during virus infection remains unknown. We investigated the frequency of HLA-G + MDSCs and its subsets in patients infected with chronic hepatitis B (CHB). In this study, frequencies of peripheral MDSCs (Lin1-HLA-DR-CD33 + CD11b + ) and HLA-G expressing subsets from 50 CHB patients and 27 normal controls were analyzed using flow cytometry. Data revealed the median percentage of MDSCs was not significantly different between the CHB patients and controls (0.30% vs. 0.29%; p=0.884). Among MDSCs, similar frequency was observed for CD14+ monocytic MDSC (mMDSCs; 31.25% vs. 23.35%; p=0.063) and CD15 + granulocytic MDSC (gMDSCs; 22.60% vs. 21.55%; p=0.558) between the two groups. However, HLA-G + MDSCs was significantly increased in CHB patients compared with that of controls (3.30% vs. 0.50%; p<0.001). Furthermore, both HLA-G + mMDSCs (0.99% vs. 0.00%; p<0.001) and HLA-G + gMDSC (0.78% vs. 0.00%; p<0.001) were also dramatically increased in CHB patients. Particularly, HLA-G + gMDSC was inversely correlated to the viral DNA loads and significantly increased in HBeAb positive patients. Summary, this work reports for the first time HLA-G + MDSCs, a new population of peripheral MDSCs, were expanded in CHB patients; however, its clinical relevance yet to be further explored.

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The role of HLA-G in immunity and hematopoiesis

Cited by 57 publications

References 171 publications

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

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