المؤلفون: N. M. Lazareva, I. V. Kudryavtsev, O. P. Baranova, D. V. Isakov, M. K. Serebriakova, A. A. Bazhanov, N. A. Arsentieva, N. E. Liubimova, T. P. Ses’, M. M. Ilkovich, A. A. Totolian

المصدر: Медицинская иммунология, Vol 25, Iss 5, Pp 1049-1058 (2023)

مصطلحات موضوعية: sarcoidosis, cd4+ t cells, th cell differentiation, th17 cell subsets, flow cytometry, cytokines, Immunologic diseases. Allergy, RC581-607

الوصف: Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme.

وصف الملف: electronic resource

العلاقة: https://www.mimmun.ru/mimmun/article/view/2694Test; https://doaj.org/toc/1563-0625Test; https://doaj.org/toc/2313-741XTest

الوصول الحر: https://doaj.org/article/262bf29d573e44e2aef43c438dac5fa2Test

المؤلفون: I. V. Kudryavtsev, N. M. Lazareva, O. P. Baranova, M. K. Serebriakova, T. P. Ses’, M. M. Ilkovich, A. A. Totolian

المصدر: Медицинская иммунология, Vol 24, Iss 3, Pp 573-586 (2022)

مصطلحات موضوعية: sarcoidosis, cd4+t cells, th cell differentiation, th17 cell subsets, th17.1, flow cytometry, Immunologic diseases. Allergy, RC581-607

الوصف: Sarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, and non-Lofgren’s syndrome (nLS) is a chronic type of disease with a high risk of pulmonary fibrosis. Our study was aimed to investigate the balance of main “polarized” CD4+ central and effector memory T cells from treatment-naive patients with pulmonary sarcoidosis (LS (n = 19) and nLS (n = 63)) compared to healthy volunteers (HC, n = 48). This marker might be used as immunological markers for predicting severity of this disorder. Multicolor flow cytometry analysis demonstrated that the patients with nLS showed significantly low levels of relative and absolute numbers of CD3+CD4+ lymphocytes if compared to patients with LS and control group (38.94% (31.33-44.24) versus 48.96% (43.34-53.54) and 47.63% (43.82-52.73), p < 0.001 in both cases). Moreover, patients with nLS had reduced frequencies and absolute numbers of “naive”, CM and EM Th cells if compared with healthy controls. Furthermore, the patients with LS showed increased relative and absolute numbers of peripheral blood EM Th cells, capable for migration to peripheral inflamed tissues, when compared with nLS. Finally, patients with LS had increased frequencies and absolute numbers of effector TEMRA Th cells as compared to HC and nLS. Next, significant differences Th1 and Th2 cells frequencies were shown between the patients with nLS and HC (9.64% (7.06-13.65) versus 13.80% (11.24-18.03) with p < 0.001, and 11.96% (9.86-14.78) versus 10.67% (9.13-12.98) with p = 0.048, respectively). But there were no significant differences in the relative numbers of CXCR5-CCR6+Th17 and CXCR5+ follicular T helper cells (Tfh) between the groups. Finally, both groups of patients with pulmonary sarcoidosis contained low proportions of “non-classical” Th17 and DN Th17 cell, but increased levels of DP Th17 cells within total CXCR5-CCR6+ CM Th if compared with HC. Nevertheless, patients with nLS had increased frequency of “classical” Th17 in comparison with healthy controls. A very similar imbalance between different Th17 cell subsets was observed within total CXCR5CCR6+ effector memory Th, that were able to migrate from the bloodstream to the sites of infection, or tissue injury. Taken together, the data suggest that the proportions of Th17 cell subsets in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and these cells could serve as a new therapeutic target.

وصف الملف: electronic resource

العلاقة: https://www.mimmun.ru/mimmun/article/view/2468Test; https://doaj.org/toc/1563-0625Test; https://doaj.org/toc/2313-741XTest

الوصول الحر: https://doaj.org/article/7e83a774cb6040d2a4f270116a3d1422Test

المؤلفون: Judith Schick, Meltem Altunay, Matthew Lacorcia, Nathalie Marschner, Stefanie Westermann, Julia Schluckebier, Christoph Schubart, Barbara Bodendorfer, Dennis Christensen, Christian Alexander, Stefan Wirtz, David Voehringer, Clarissa Prazeres da Costa, Roland Lang

المصدر: eLife, Vol 12 (2023)

مصطلحات موضوعية: co-infection, Th cell differentiation, Nippostrongylus brasiliensis, Schistosoma mansoni, mycobacterial cord factor, C-type lectin receptors, Medicine, Science, Biology (General), QH301-705.5

الوصف: The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6’-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematode Nippostrongylus brasiliensis in monocytes. To determine the impact of helminth infection on MINCLE-dependent immune responses, we vaccinated mice with a recombinant protein together with the MINCLE ligand trehalose-6,6-dibehenate (TDB) as adjuvant. Concurrent infection with N. brasiliensis or with Schistosoma mansoni promoted T cell-derived IL-4 production and suppressed Th1/Th17 differentiation in the spleen. In contrast, helminth infection did not reduce Th1/Th17 induction by TDB in draining peripheral lymph nodes, where IL-4 levels were unaltered. Upon use of the TLR4-dependent adjuvant G3D6A, N. brasiliensis infection impaired selectively the induction of splenic antigen-specific Th1 but not of Th17 cells. Inhibition of MINCLE-dependent Th1/Th17 responses in mice infected with N. brasiliensis was dependent on IL-4/IL-13. Thus, helminth infection attenuated the Th17 response to MINCLE-dependent immunization in an organ- and adjuvant-specific manner via the Th2 cytokines IL-4/IL-13. Taken together, our results demonstrate downregulation of MINCLE expression on monocytes and macrophages by IL-4 as a possible mechanism of thwarted Th17 vaccination responses by underlying helminth infection.

وصف الملف: electronic resource

العلاقة: https://elifesciences.org/articles/72923Test; https://doaj.org/toc/2050-084XTest

الوصول الحر: https://doaj.org/article/5ae7b59983a44ed9bd8dcf86dc279bbfTest

المؤلفون: Difeng Fang, Ayanna Healy, Jinfang Zhu

المصدر: Frontiers in Immunology, Vol 13 (2023)

مصطلحات موضوعية: lineage-determining transcription factor, epigenetic modification, CD4 T helper cells, innate lymphoid cells, Th cell differentiation, ILC development, Immunologic diseases. Allergy, RC581-607

الوصف: CD4 T helper (Th) cell subsets, including Th1, Th2 and Th17 cells, and their innate counterparts innate lymphoid cell (ILC) subsets consisting of ILC1s, ILC2s and ILC3s, display similar effector cytokine-producing capabilities during pro-inflammatory immune responses. These lymphoid cell subsets utilize the same set of lineage-determining transcription factors (LDTFs) for their differentiation, development and functions. The distinct ontogeny and developmental niches between Th cells and ILCs indicate that they may adopt different external signals for the induction of LDTF during lineage commitment. Increasing evidence demonstrates that many conserved cis-regulatory elements at the gene loci of LDTFs are often preferentially utilized for the induction of LDTF expression during Th cell differentiation and ILC development at different stages. In this review, we discuss the functions of lineage-related cis-regulatory elements in inducing T-bet, GATA3 or RORγt expression based on the genetic evidence provided in recent publications. We also review and compare the upstream signals involved in LDTF induction in Th cells and ILCs both in vitro and in vivo. Finally, we discuss the possible mechanisms and physiological importance of regulating LDTF dynamic expression during ILC development and activation.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1081153/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/3d176d2164dc44ebb1b600bd97e51613Test

المؤلفون: D. Alejandro Canaria, Maia G. Clare, Bingyu Yan, Charlotte B. Campbell, Zachariah A. Ismaio, Nicole L. Anderson, Sungtae Park, Alexander L. Dent, Majid Kazemian, Matthew R. Olson

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: Th cell differentiation, IL-9 cytokine, IL-2 signaling, nuclear factor-kB, Th9 cells, Immunologic diseases. Allergy, RC581-607

الوصف: IL-9-producing CD4+ T helper cells, termed Th9 cells, differentiate from naïve precursor cells in response to a combination of cytokine and cell surface receptor signals that are elevated in inflamed tissues. After differentiation, Th9 cells accumulate in these tissues where they exacerbate allergic and intestinal disease or enhance anti-parasite and anti-tumor immunity. Previous work indicates that the differentiation of Th9 cells requires the inflammatory cytokines IL-4 and TGF-β and is also dependent of the T cell growth factor IL-2. While the roles of IL-4 and TGF-β-mediated signaling are relatively well understood, how IL-2 signaling contributes to Th9 cell differentiation outside of directly inducing the Il9 locus remains less clear. We show here that murine Th9 cells that differentiate in IL-2-limiting conditions exhibit reduced IL-9 production, diminished NF-kB activation and a reduced NF-kB-associated transcriptional signature, suggesting that IL-2 signaling is required for optimal NF-kB activation in Th9 cells. Interestingly, both IL-9 production and the NF-kB transcriptional signature could be rescued by addition of the NF-kB-activating cytokine IL-1β to IL-2-limiting cultures. IL-1β was unique among NF-kB-activating factors in its ability to rescue Th9 differentiation as IL-2 deprived Th9 cells selectively induced IL-1R expression and IL-1β/IL-1R1 signaling enhanced the sensitivity of Th9 cells to limiting amounts of IL-2 by suppressing expression of the Th9 inhibitory factor BCL6. These data shed new light on the intertwined nature of IL-2 and NF-kB signaling pathways in differentiating Th cells and elucidate the potential mechanisms that promote Th9 inflammatory function in IL-2-limiting conditions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032618/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/f8a357bbff2a4fd8819701a96855a258Test

المؤلفون: Ewa Kuca-Warnawin, Magdalena Plebańczyk, Marzena Ciechomska, Marzena Olesińska, Piotr Szczęsny, Ewa Kontny

المصدر: International Journal of Molecular Sciences; Volume 23; Issue 10; Pages: 5317

مصطلحات موضوعية: systemic lupus erythematosus, systemic sclerosis, adipose-derived mesenchymal stem cells, Th-cell differentiation

جغرافية الموضوع: agris

الوصف: Complex pathogenesis of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is associated with an imbalance of various Th-cell subpopulations. Mesenchymal stem cells (MSCs) have the ability to restore this balance. However, bone marrow-derived MSCs of SLE and SSc patients exhibit many abnormalities, whereas the properties of adipose derived mesenchymal stem cells (ASCS) are much less known. Therefore, we examined the effect of ASCs obtained from SLE (SLE/ASCs) and SSc (SSc/ASCs) patients on Th subset differentiation, using cells from healthy donors (HD/ASCs) as controls. ASCs were co-cultured with activated CD4+ T cells or peripheral blood mononuclear cells. Expression of transcription factors defining Th1, Th2, Th17, and regulatory T cell (Tregs) subsets, i.e., T-bet, GATA3, RORc, and FoxP3, were analysed by quantitative RT-PCR, the concentrations of subset-specific cytokines were measured by ELISA, and Tregs formation by flow cytometry. Compared with HD/ASCs, SLE/ASCs and especially SSc/ASCs triggered Th differentiation which was disturbed at the transcription levels of genes encoding Th1- and Tregs-related transcription factors. However, we failed to find functional consequences of this abnormality, because all tested ASCs similarly switched differentiation from Th1 to Th2 direction with accompanying IFNγ/IL-4 ratio decrease, up-regulated Th17 formation and IL-17 secretion, and up-regulated classical Tregs generation.

وصف الملف: application/pdf

العلاقة: Molecular Immunology; https://dx.doi.org/10.3390/ijms23105317Test

الإتاحة: https://doi.org/10.3390/ijms23105317Test

المؤلفون: Canaria, D. Alejandro, Clare, Maia G., Yan, Bingyu, Campbell, Charlotte B., Ismaio, Zachariah A., Anderson, Nicole L., Park, Sungtae, Dent, Alexander L., Kazemian, Majid, Olson, Matthew R.

المساهمون: Microbiology and Immunology, School of Medicine

المصدر: PMC

مصطلحات موضوعية: Th cell differentiation, IL-9 cytokine, IL-2 signaling, Nuclear factor-kB, Th9 cells

الوصف: IL-9-producing CD4+ T helper cells, termed Th9 cells, differentiate from naïve precursor cells in response to a combination of cytokine and cell surface receptor signals that are elevated in inflamed tissues. After differentiation, Th9 cells accumulate in these tissues where they exacerbate allergic and intestinal disease or enhance anti-parasite and anti-tumor immunity. Previous work indicates that the differentiation of Th9 cells requires the inflammatory cytokines IL-4 and TGF-β and is also dependent of the T cell growth factor IL-2. While the roles of IL-4 and TGF-β-mediated signaling are relatively well understood, how IL-2 signaling contributes to Th9 cell differentiation outside of directly inducing the Il9 locus remains less clear. We show here that murine Th9 cells that differentiate in IL-2-limiting conditions exhibit reduced IL-9 production, diminished NF-kB activation and a reduced NF-kB-associated transcriptional signature, suggesting that IL-2 signaling is required for optimal NF-kB activation in Th9 cells. Interestingly, both IL-9 production and the NF-kB transcriptional signature could be rescued by addition of the NF-kB-activating cytokine IL-1β to IL-2-limiting cultures. IL-1β was unique among NF-kB-activating factors in its ability to rescue Th9 differentiation as IL-2 deprived Th9 cells selectively induced IL-1R expression and IL-1β/IL-1R1 signaling enhanced the sensitivity of Th9 cells to limiting amounts of IL-2 by suppressing expression of the Th9 inhibitory factor BCL6. These data shed new light on the intertwined nature of IL-2 and NF-kB signaling pathways in differentiating Th cells and elucidate the potential mechanisms that promote Th9 inflammatory function in IL-2-limiting conditions.

وصف الملف: application/pdf

العلاقة: Frontiers in Immunology; Canaria DA, Clare MG, Yan B, et al. IL-1β promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6. Front Immunol. 2022;13:1032618. Published 2022 Nov 1. doi:10.3389/fimmu.2022.1032618; https://hdl.handle.net/1805/35863Test

الإتاحة: https://doi.org/10.3389/fimmu.2022.1032618Test
https://hdl.handle.net/1805/35863Test

المؤلفون: Xinxing Zhang, Xin Zhao, Huiming Sun, Yongdong Yan, Li Huang, Wenjin Gu, Wujun Jiang, Yuqing Wang, Canhong Zhu, Wei Ji, Chuangli Hao, Zhengrong Chen

المصدر: Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-10 (2018)

مصطلحات موضوعية: Asthma, Children, MircoRNA, B7-H3, Th cell differentiation, Medicine

الوصف: Abstract Background MicroRNAs play roles in the pathogenesis of bronchial asthma. However, the mechanism of miR-29c in allergic asthma remains unclear. This study is to elucidate the regulation of Th cell differentiation by miR-29c in mononuclear macrophages. Methods A total of 52 children with asthma exacerbation and 26 children as controls were enrolled in the study. CD14+ monocytes were isolated from the peripheral blood. Differential expressions of microRNAs were evaluated using microarray analysis and miR-29c expression in monocytes was determined by qRT-PCR. The plasma B7-H3 was determined by ELISA. Transfection studies and luciferase reporter assay were performed to confirm target gene of miR-29c and its function. Results Compared to controls, 88 miRNAs in blood monocytes were up-regulated and 41 miRNAs down-regulated including miR-29c in asthma children. Children with asthma exacerbation had significantly lower level of miR-29c and higher level of plasma B7-H3 compared to controls (both P

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12967-018-1590-8Test; https://doaj.org/toc/1479-5876Test

الوصول الحر: https://doaj.org/article/b0c20ec3954d4e498e8927ee30b36816Test

المؤلفون: perdicchio, M. (Maurizio), Ilarregui, J. (Juan), Verstege, I. (Marleen), Cornelissen, A.M. (Lenneke), Schetters, T.T. (Sjoerd), Engels, S. (Steef), Ambrosini, M. (Martino), Kalay, H. (Hakan), Veninga, H. (Henrike), Haan, M.M. (Joke) den, Berkel, L.A. (Lisette) van, Samsom, J.N. (Janneke), Crocker, P.R. (Paul), Sparwasser, T. (Tim), Berod, L. (Luciana), Garcia-Vallejo, J. (Juan), Kooyk, Y. (Yvette) van, Unger, W.W.J. (Wendy)

المصدر: Proceedings of the National Academy of Sciences of the United States of America vol. 113 no. 12, pp. 3329-3334

مصطلحات موضوعية: Mice, Dendritic Cells, Antibodies, Modification of Antigens with Sialylated Glycans, Th-Cell Differentiation and Testing of Suppressive Capacity, Cytokine Analysis, In Vivo Treatment, Confocal Microscopy and Imaging Flow Cytometry, Statistical Analysis

الوصف: Sialic acids are negatively charged nine-carbon carboxylated monosaccharides that often cap glycans on glycosylated proteins and lipids. Because of their strategic location at the cell surface, sialic acids contribute to interactions that are critical for immune homeostasis via interactions with sialic acid-binding Ig-type lectins (siglecs). In particular, these interactions may be of importance in cases where sialic acids may be overexpressed, such as on certain pathogens and tumors. We now demonstrate that modification of antigens with sialic acids (Sia-antigens) regulates the generation of antigen-specific regulatory T (Treg) cells via dendritic cells (DCs). Additionally, DCs that take up Sia-antigen prevent formation of effector CD4+ and CD8+ T cells. Importantly, the regulatory properties endowed on DCs upon Sia-antigen uptake are antigen-specific: only T cells responsive to the sialylated antigen become tolerized. In vivo, injection of Sia-antigen–loaded DCs increased de novo Treg-cell numbers and dampened effector T-cell expansion and IFN-γ production. The dual tolerogenic features that Sia-antigen imposed on DCs are Siglec-E–mediated and maintained under inflammatory conditions. Moreover, loading DCs with Sia-antigens not only inhibited the function of in vitro–established Th1 and Th17 effector T cells but also significantly dampened ex vivo myelin-reactive T cells, present in the circulation of mice with experimental autoimmune encephalomyelitis. These data indicate that sialic acid-modified antigens instruct DCs in an antigen-specific tolerogenic programming, enhancing Treg cells and reducing the generation and propagation of inflammatory T cells. Our data suggest that sialylation of antigens provides an attractive way to induce antigen-specific immune tolerance.

العلاقة: http://repub.eur.nl/pub/79924Test; urn:hdl:1765/79924

الإتاحة: https://doi.org/10.1073/pnas.1507706113Test
http://repub.eur.nl/pub/79924Test

المؤلفون: Wenjin Gu, Li Huang, Xin Zhao, Zhengrong Chen, Yuqing Wang, Wujun Jiang, Chuangli Hao, Canhong Zhu, Huiming Sun, Xinxing Zhang, Wei Ji, Yongdong Yan

المصدر: Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-10 (2018)
Journal of Translational Medicine

مصطلحات موضوعية: 0301 basic medicine, Male, B7 Antigens, THP-1 Cells, Cellular differentiation, lcsh:Medicine, Th cell differentiation, Pathogenesis, 0302 clinical medicine, Patient Admission, Genes, Reporter, Child, Luciferases, Children, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, MircoRNA, Cell Differentiation, General Medicine, Transfection, T-Lymphocytes, Helper-Inducer, Patient Discharge, B7-H3, Disease Progression, Female, Signal Transduction, CD14, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, microRNA, medicine, Hypersensitivity, Humans, Asthma, Base Sequence, business.industry, Research, Gene Expression Profiling, Macrophages, lcsh:R, medicine.disease, Coculture Techniques, Gene expression profiling, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Immunology, business, 030215 immunology

الوصف: Background MicroRNAs play roles in the pathogenesis of bronchial asthma. However, the mechanism of miR-29c in allergic asthma remains unclear. This study is to elucidate the regulation of Th cell differentiation by miR-29c in mononuclear macrophages. Methods A total of 52 children with asthma exacerbation and 26 children as controls were enrolled in the study. CD14+ monocytes were isolated from the peripheral blood. Differential expressions of microRNAs were evaluated using microarray analysis and miR-29c expression in monocytes was determined by qRT-PCR. The plasma B7-H3 was determined by ELISA. Transfection studies and luciferase reporter assay were performed to confirm target gene of miR-29c and its function. Results Compared to controls, 88 miRNAs in blood monocytes were up-regulated and 41 miRNAs down-regulated including miR-29c in asthma children. Children with asthma exacerbation had significantly lower level of miR-29c and higher level of plasma B7-H3 compared to controls (both P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cdb046bb4f11e273fa4785ef544ec78Test
http://link.springer.com/article/10.1186/s12967-018-1590-8Test