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1.
Adv Immunol ; 144: 155-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31699216

RESUMO

B-cell follicle represents a functionally dynamic microstructure within second lymphoid tissues, predominantly consisting of B cells, follicular T cells and DCs. Through intimate interactions with cognate B cells, follicular helper T cells (Tfh) initiate and facilitate germinal center (GC) reactions by providing signals required for producing high-affinity antibodies, as well as for the generation of long-lived antibody-secreting plasma cells and memory B cells. Concomitantly, germinal center reaction needs to be fine controlled to avoid autoimmunity or B-cell malignancies. Among immune cells residing in follicles, follicular regulatory T cells (Tfr), converted from naïve Treg cells, are specifically assigned to repress excessive GC responses by suppressing Tfh and GC B cells within GC structure. Hence, through Yin and Yang (positive and negative) regulation of GC reaction, Tfh cells play concert with Tfr cells in maintaining immune homeostasis. Besides CD4+ T cells, a small portion of CXCR5 expressing CD8+ T cells, regarded as follicular cytotoxic T cells (Tfc), could migrate into B cell follicles during chronic viral infection and several types of cancers, and this population exhibit lower level of exhaustion than its CXCR5- counterparts. Besides, Tfc cells demonstrate a stem-cell like phenotype during chronic infection which could further differentiate into terminally differentiated CXCR5-CD8+ T cells. Collectively, in this review, we will discuss the recent advances in our understanding of the ontology and differentiation of B-cell follicle resident Tfh, Tfr and Tfc cells.

2.
Am J Transl Res ; 11(6): 3722-3736, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312383

RESUMO

T follicular helper (TFH) cells are crucial for effective humoral immunity by providing the required signals to cognate B cells and promoting germinal center (GC) formation. Many intrinsic and extrinsic factors have been reported to be involved in the multistage, multifactorial differentiation process of TFH cells. By comparing gene expression between TFH cells and TH1 cells based on published GEO data, we found selective and high expression of sclerostin domain-containing protein 1 (SOSTDC1) in TFH cells but not in TH1 cells; however, it is unclear whether SOSTDC1 is important for the differentiation and/or function of TFH cells. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we confirmed the selective expression of SOSTDC1 in TFH cells compared to that in TH1 cells, but the ablation of SOSTDC1 did not affect TFH cell differentiation or effector function. Thus, our results indicate that the SOSTDC1 protein is merely a specific marker of TFH cells but does not play a functional role in the differentiation of TFH cells during acute viral infection.

3.
Front Immunol ; 10: 606, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984183

RESUMO

Follicular helper T cells (TFH cells), known as the primary "helpers" of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively). These features likely indicate both the lineage-specificity and environmental adaption of the TFH cell responses. However, the extent to which the TFH cell response relies on these environmentally specific TFs is not completely understood. Here, we found that T-bet was specifically expressed in Type I TFH cells but not Type II TFH cells. While dispensable for the early fate commitment of TFH cells, T-bet was essential for the maintenance of differentiated TFH cells, promoting their proliferation, and inhibiting their apoptosis during acute viral infection. Microarray analysis showed both similarities and differences in transcriptome dependency on T-bet in TFH and TH1 cells, suggesting the distinctive role of T-bet in TFH cells. Collectively, our findings reveal an important and specific supporting role for T-bet in type I TFH cell response, which can help us gain a deeper understanding of TFH cell subsets.

4.
Cell Mol Immunol ; 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842630

RESUMO

Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.

5.
Front Immunol ; 10: 249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828337

RESUMO

During viral infection, virus-specific follicular helper T cells provide important help to cognate B cells for their survival, consecutive proliferation and mutation and eventual differentiation into memory B cells and antibody-secreting plasma cells. Similar to Tfh cells generated in other conditions, the differentiation of virus-specific Tfh cells can also be characterized as a process involved multiple factors and stages, however, which also exhibits distinct features. Here, we mainly focus on the current understanding of Tfh fate commitment, functional maturation, lineage maintenance and memory transition and formation in the context of viral infection.

6.
Front Immunol ; 10: 169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814995

RESUMO

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

7.
Methods Mol Biol ; 1707: 95-109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29388102

RESUMO

B lymphocytes and their differentiated daughter cells are charged with responding to invading pathogens and producing protective antibodies against these pathogens. The physiology of B cells is intimately connected with the function of the B cell antigen receptor (BCR). Upon activation of BCR, transmembrane signals are generated, and several downstream pathways are activated, which provide a primary directive for the cell's subsequent response. mTOR is a serine/threonine kinase that controls cell proliferation and metabolism in response to a diverse range of extracellular stimuli. The activation of mTOR signaling downstream of PI3K/Akt activity by B cell receptor (BCR) engagement has been generally assumed to be essential for B cell responses. This chapter seeks to present two protocols to evaluate mTOR activity in B cells bearing BCR specific to 4-hydroxy-3-nitrophenylacetyl (NP)-hapten.


Assuntos
Linfócitos B/imunologia , Citometria de Fluxo/métodos , Receptores de Antígenos de Linfócitos B/imunologia , Transdução de Sinais/imunologia , Serina-Treonina Quinases TOR/imunologia , Animais , Linfócitos B/citologia , Haptenos/imunologia , Haptenos/farmacologia , Camundongos , Nitrofenóis/farmacologia , Fenilacetatos/farmacologia , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Transdução de Sinais/efeitos dos fármacos
8.
Immunity ; 47(3): 538-551.e5, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28930662

RESUMO

Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation. Mechanistically, mTORC1-mediated phosphorylation of the transcription factor STAT3 induced the expression of the transcription factor TCF-1 by promoting STAT3 binding to the Tcf7 5'-regulatory region. Subsequently, TCF-1 bound to the Bcl6 promoter to induce Bcl6 expression, which launched the Tfr cell differentiation program. Thus, mTORC1 initiates Tfr cell differentiation by activating the TCF-1-Bcl-6 axis during immunization or infection.


Assuntos
Imunomodulação , Complexos Multiproteicos/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Biomarcadores , Diferenciação Celular/imunologia , Análise por Conglomerados , Perfilação da Expressão Gênica , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Imunização , Imunofenotipagem , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Transgênicos , Complexos Multiproteicos/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/citologia , Serina-Treonina Quinases TOR/genética
9.
Immunology ; 152(2): 276-286, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28557002

RESUMO

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that has been shown to be essential for the differentiation and function of various immune cells. Earlier in vitro studies showed that mTOR signalling regulates B-cell biology by supporting their activation and proliferation. However, how mTOR signalling temporally regulates in vivo germinal centre B (GCB) cell development and differentiation into short-lived plasma cells, long-lived plasma cells and memory cells is still not well understood. In this study, we used a combined conditional/inducible knock-out system to investigate the temporal regulation of mTOR complex 1 (mTORC1) in the GCB cell response to acute lymphocytic choriomeningitis virus infection by deleting Raptor, a main component of mTORC1, specifically in B cells in pre- and late GC phase. Early Raptor deficiency strongly inhibited GCB cell proliferation and differentiation and plasma cell differentiation. Nevertheless, late GC Raptor deficiency caused only decreases in the size of memory B cells and long-lived plasma cells through poor maintenance of GCB cells, but it did not change their differentiation. Collectively, our data revealed that mTORC1 signalling supports GCB cell responses at both early and late GC phases during viral infection but does not regulate GCB cell differentiation into memory B cells and plasma cells at the late GC stage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos B/enzimologia , Centro Germinativo/enzimologia , Coriomeningite Linfocítica/enzimologia , Vírus da Coriomeningite Linfocítica/imunologia , Complexos Multiproteicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/transplante , Linfócitos B/virologia , Transplante de Medula Óssea , Diferenciação Celular , Proliferação de Células , Modelos Animais de Doenças , Predisposição Genética para Doença , Centro Germinativo/imunologia , Centro Germinativo/virologia , Interações Hospedeiro-Patógeno , Imunidade Humoral , Memória Imunológica , Ativação Linfocitária , Coriomeningite Linfocítica/genética , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexos Multiproteicos/deficiência , Complexos Multiproteicos/genética , Complexos Multiproteicos/imunologia , Fenótipo , Plasmócitos/enzimologia , Plasmócitos/imunologia , Plasmócitos/virologia , Proteína Regulatória Associada a mTOR , Transdução de Sinais , Serina-Treonina Quinases TOR/deficiência , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/imunologia , Fatores de Tempo , Quimeras de Transplante
10.
Sci Adv ; 1(10): e1500886, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26702440

RESUMO

Redox flow batteries (RFBs) are considered one of the most promising large-scale energy storage technologies. However, conventional RFBs suffer from low energy density due to the low solubility of the active materials in electrolyte. On the basis of the redox targeting reactions of battery materials, the redox flow lithium battery (RFLB) demonstrated in this report presents a disruptive approach to drastically enhancing the energy density of flow batteries. With LiFePO4 and TiO2 as the cathodic and anodic Li storage materials, respectively, the tank energy density of RFLB could reach ~500 watt-hours per liter (50% porosity), which is 10 times higher than that of a vanadium redox flow battery. The cell exhibits good electrochemical performance under a prolonged cycling test. Our prototype RFLB full cell paves the way toward the development of a new generation of flow batteries for large-scale energy storage.

11.
Autophagy ; 11(11): 1998-2013, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26491898

RESUMO

FGFR3 (fibroblast growth factor receptor 3) is a negative regulator of endochondral ossification. Gain-of-function mutations in FGFR3 are responsible for achondroplasia, the most common genetic form of dwarfism in humans. Autophagy, an evolutionarily conserved catabolic process, maintains chondrocyte viability in the growth plate under stress conditions, such as hypoxia and nutritional deficiencies. However, the role of autophagy and its underlying molecular mechanisms in achondroplasia remain elusive. In this study, we found activated FGFR3 signaling inhibited autophagic activity in chondrocytes, both in vivo and in vitro. By employing an embryonic bone culture system, we demonstrated that treatment with autophagy inhibitor 3-MA or chloroquine led to cartilage growth retardation, which mimics the effect of activated-FGFR3 signaling on chondrogenesis. Furthermore, we found that FGFR3 interacted with ATG12-ATG5 conjugate by binding to ATG5. More intriguingly, FGFR3 signaling was found to decrease the protein level of ATG12-ATG5 conjugate. Consistently, using in vitro chondrogenic differentiation assay system, we showed that the ATG12-ATG5 conjugate was essential for the viability and differentiation of chondrocytes. Transient transfection of ATG5 partially rescued FGFR3-mediated inhibition on chondrocyte viability and differentiation. Our findings reveal that FGFR3 inhibits the autophagic activity by decreasing the ATG12-ATG5 conjugate level, which may play an essential role in the pathogenesis of achondroplasia.

12.
Nat Immunol ; 16(9): 991-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26214740

RESUMO

Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of T(FH) differentiation and the effector function of differentiated T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T(FH) cells during acute viral infection.


Assuntos
Diferenciação Celular/imunologia , Proteínas de Ligação a DNA/imunologia , Fator 1-alfa Nuclear de Hepatócito/imunologia , Infecções por Orthomyxoviridae/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Fatores de Transcrição/imunologia , Animais , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Vírus da Influenza A , Camundongos , Camundongos Knockout , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Proto-Oncogênicas c-bcl-6 , Linfócitos T Auxiliares-Indutores/metabolismo , Fatores de Transcrição/genética
13.
PLoS Genet ; 11(6): e1005214, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26091072

RESUMO

Most cartilaginous tumors are formed during skeletal development in locations adjacent to growth plates, suggesting that they arise from disordered endochondral bone growth. Fibroblast growth factor receptor (FGFR)3 signaling plays essential roles in this process; however, the role of FGFR3 in cartilaginous tumorigenesis is not known. In this study, we found that postnatal chondrocyte-specific Fgfr3 deletion induced multiple chondroma-like lesions, including enchondromas and osteochondromas, adjacent to disordered growth plates. The lesions showed decreased extracellular signal-regulated kinase (ERK) activity and increased Indian hedgehog (IHH) expression. The same was observed in Fgfr3-deficient primary chondrocytes, in which treatment with a mitogen-activated protein kinase (MEK) inhibitor increased Ihh expression. Importantly, treatment with an inhibitor of IHH signaling reduced the occurrence of chondroma-like lesions in Fgfr3-deficient mice. This is the first study reporting that the loss of Fgfr3 function leads to the formation of chondroma-like lesions via downregulation of MEK/ERK signaling and upregulation of IHH, suggesting that FGFR3 has a tumor suppressor-like function in chondrogenesis.


Assuntos
Condroma/metabolismo , Proteínas Hedgehog/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Regulação para Cima , Animais , Linhagem Celular , Células Cultivadas , Condrócitos/metabolismo , Condroma/genética , Proteínas Hedgehog/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/deficiência , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
14.
Chem Commun (Camb) ; 51(46): 9451-4, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-25960290

RESUMO

A redox flow lithium-oxygen battery (RFLOB) by using soluble redox catalysts with good performance was demonstrated for large-scale energy storage. The new device enables the reversible formation and decomposition of Li2O2 via redox targeting reactions in a gas diffusion tank, spatially separated from the electrode, which obviates the passivation and pore clogging of the cathode.

15.
ACS Appl Mater Interfaces ; 5(13): 6292-9, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23751248

RESUMO

A nickel salt-urea-H2O ternary system has been developed for the large-scale synthesis of hierarchical α-Ni(OH)2 microspheres, the solid precursor for the subsequent topotactic transition to NiO upon calcination. In this facile synthetic system, hierarchical structure is self-assembled under the cooperative direction of urea and anions in nickel salts. Thus, simply tuning the Ni salts leads to the selective construction of urchin and flowerlike hierarchical α-Ni(OH)2 and NiO microspheres consisting of radial 1D nanowires and 2D nanoplates, respectively. The obtained NiO microspheres possessing accessible nanopores, excellent structural stability and large surface area up to 130 m(2)/g show promising electrochemical performance in anodic lithium storage for lithium-ion battery.

16.
Phys Chem Chem Phys ; 15(6): 1793-7, 2013 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-23262995

RESUMO

Reversible chemical delithiation/lithiation of LiFePO(4) was successfully demonstrated using ferrocene derivatives, based on which a novel energy storage system--the redox flow lithium-ion battery (RFLB), was devised by integrating the operation flexibility of a redox flow battery and high energy density of a lithium-ion battery. Distinct from the recent semi-solid lithium rechargeable flow battery, the energy storage materials of RFLB stored in separate energy tanks remain stationary upon operation, giving us a fresh perspective on building large-scale energy storage systems with higher energy density and improved safety.

17.
Hum Immunol ; 72(9): 733-40, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21708203

RESUMO

In the present study, 17 killer cell immunoglobulin-like receptors (KIR) genes and KIR ligands (human leukocyte antigen [HLA] -A and -B) were detected by using a polymerase chain reaction-sequence-specific primer (PCR-SSP) method in 104 unrelated healthy Han individuals living in Shaanxi province, China. The observed carrier frequencies of the 12 KIR genes ranged from 0.14 to 0.96. KIR2DL4, 3DL2, 3DL3, 2DP1 and 3DP1 were found to be present in every individual. A total of 51 different KIR gene profiles were identified, in which 11 gene profiles exclusively belonged to the study population. Neighbor-joining phylogenetic tree between the studing population and its neighboring ethnic groups was constructed using the observed carrier frequencies of 13 KIR loci. The phylogenetic tree shows that the Shaanxi Han population, Han populations in different regions, Yi, Japanese, and Koreans were in the same cluster. KIR/HLA relationships show that KIR3DS1(-)/3DL1(+)/Bw4(+) was the most common association in the population. In conclusion, the present study findings reveal the high polymorphism of KIRs in the Shaanxi Han population, demonstrate the KIR/HLA association in the study population, and enrich the KIR and HLA gene resources. The obtained KIR data will further the understanding of genetic relationships among populations in different geographic areas, and assist in answering questions regarding KIR/HLA relationships.


Assuntos
Grupos Étnicos , Antígenos HLA-A/genética , Receptores KIR/genética , China , Frequência do Gene , Genética Populacional , Técnicas de Genotipagem , Haplótipos/genética , Humanos , Filogenia , Polimorfismo Genético
18.
PLoS One ; 5(11): e13458, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21079793

RESUMO

BACKGROUND: Previous studies indicate that the frequency distributions of HLA alleles and haplotypes vary from one ethnic group to another or between the members of the same ethnic group living in different geographic areas. It is necessary and meaningful to study the high-resolution allelic and haplotypic distributions of HLA loci in different groups. METHODOLOGY/PRINCIPAL FINDINGS: High-resolution HLA typing for the Uyghur ethnic minority group using polymerase chain reaction-sequence-based-typing method was first reported. HLA-A, -B and -DRB1 allelic distributions were determined in 104 unrelated healthy Uyghur individuals and haplotypic frequencies and linkage disequilibrium parameters for HLA loci were estimated using the maximum-likelihood method. A total of 35 HLA-A, 51 HLA-B and 33 HLA-DRB1 alleles were identified at the four-digit level in the population. High frequency alleles were HLA-A*1101 (13.46%), A*0201 (12.50%), A*0301 (10.10%); HLA-B*5101(8.17%), B*3501(6.73%), B*5001 (6.25%); HLA-DRB1*0701 (16.35%), DRB1*1501 (8.65%) and DRB1*0301 (7.69%). The two-locus haplotypes at the highest frequency were HLA-A*3001-B*1302 (2.88%), A*2402-B*5101 (2.86%); HLA-B*5001-DRB1*0701 (4.14%) and B*0702-DRB1*1501 (3.37%). The three-locus haplotype at the highest frequency was HLA-A*3001-B*1302-DRB1*0701(2.40%). Significantly high linkage disequilibrium was observed in six two-locus haplotypes, with their corresponding relative linkage disequilibrium parameters equal to 1. Neighbor-joining phylogenetic tree between the Uyghur group and other previously reported populations was constructed on the basis of standard genetic distances among the populations calculated using the four-digit sequence-level allelic frequencies at HLA-A, HLA-B and HLA-DRB1 loci. The phylogenetic analyses reveal that the Uyghur group belongs to the northwestern Chinese populations and is most closely related to the Xibe group, and then to Kirgiz, Hui, Mongolian and Northern Han. CONCLUSIONS/SIGNIFICANCE: The present findings could be useful to elucidate the genetic background of the population and to provide valuable data for HLA matching in clinical bone marrow transplantation, HLA-linked disease-association studies, population genetics, human identification and paternity tests in forensic sciences.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Alelos , Grupo com Ancestrais do Continente Asiático/genética , China , Frequência do Gene , Variação Genética , Genótipo , Antígenos HLA-A/classificação , Antígenos HLA-B/classificação , Antígenos HLA-DR/classificação , Cadeias HLA-DRB1 , Haplótipos , Humanos , Desequilíbrio de Ligação , Filogenia
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