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Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa
Open accessAbstract
Recent studies have demonstrated dramatic shifts in metabolic supply-and-demand ratios during inflammation, a process resulting in localized tissue hypoxia within inflammatory lesions (“inflammatory hypoxia”). As part of the adaptive immune response, T cells are recruited to sites of inflammatory hypoxia. Given the profound effects of hypoxia on gene regulation, we hypothesized that T-cell differentiation is controlled by hypoxia. To pursue this hypothesis, we analyzed the transcriptional consequences of ambient hypoxia (1% oxygen) on a broad panel of T-cell differentiation factors. Surprisingly, these studies revealed selective, robust induction of FoxP3, a key transcriptional regulator for regulatory T cells (Tregs). Studies of promoter binding or loss- and gain-of-function implicated hypoxia-inducible factor (HIF)-1α in inducing FoxP3. Similarly, hypoxia enhanced Treg abundance in vitro and in vivo. Finally, Treg-intrinsic HIF-1α was required for optimal Treg function and Hif1a –deficient Tregs failed to control T-cell–mediated colitis. These studies demonstrate that hypoxia is an intrinsic molecular cue that promotes FoxP3 expression, in turn eliciting potent anti-inflammatory mechanisms to limit tissue damage in conditions of reduced oxygen availability.
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“For instance, tumor hypoxia and/or HIFs can attract myeloid-derived suppressor cells (Corzo et al., 2010), regulatory T-cells (Clambey et al., 2012), and tumor-associated macrophages (Doedens et al., 2010;Imtiyaz et al., 2010) with immunosuppressive functions.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Clambey et al., 2012
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Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. D. L. G. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,468
Self-citationDeaglio, S., Dwyer, K. M., Gao, W., Friedman, D. J., Usheva, A., Erat, A., Chen, J., Enjyoji, K., Linden, J. M., Oukka, M., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062512 · Cited by 2,613
Eltzschig, H. K., & Carmeliet, P. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0910283 · Cited by 2,061
Self-citationTGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,928
Shi, L. Z., Wang, R., Huang, G., Vogel, P., Neale, G., Green, D. R., & Chi, H. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110278 · Cited by 1,803
Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1
Dang, E. V., Barbi, J., Yang, H.-Y., Jinasena, D., Yu, H., Zheng, Y., Bordman, Z., Fu, J., Kim, Y., Yen, H.-R., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.033 · Cited by 1,595
Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W. R., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.017 · Cited by 1,586
Foxp3+ follicular regulatory T cells control the germinal center response
Linterman, M. A., Pierson, W., Lee, S. K., Kallies, A., Kawamoto, S., Rayner, T. F., Srivastava, M., Divekar, D. P., Beaton, L., Hogan, J. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2425 · Cited by 1,292
Koch, M. A., Tucker-Heard, G., Perdue, N. R., Killebrew, J. R., Urdahl, K. B., & Campbell, D. J. (2009) · Nature Immunology · doi:10.1038/ni.1731 · Cited by 1,258
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
Zheng, Y., Josefowicz, S. Z., Chaudhry, A., Peng, X. P., Forbush, K. A., & Rudensky, A. Y. (2010) · Nature · doi:10.1038/nature08750 · Cited by 1,170
Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Yang, X. O., Nurieva, R., Martínez, G., Kang, H. S., Chung, Y., Pappu, B. P., Shah, B., Chang, S. H., Schluns, K. S., Watowich, S. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.007 · Cited by 1,169
Powrie, F., Leach, M. W., Mauze, S., Menon, S., Barcomb Caddle, L., & Coffman, R. L. (1994) · Immunity · doi:10.1016/1074-7613(94)90045-0 · Cited by 1,146
Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions
Chung, Y., Tanaka, S., Chu, F., Nurieva, R. I., Martinez, G. J., Rawal, S., Wang, Y.-H., Lim, H., Reynolds, J. M., Zhou, X.-H., et al. (2011) · Nature Medicine · doi:10.1038/nm.2426 · Cited by 1,120
McGeachy, M. J., Chen, Y., Tato, C. M., Laurence, A., Joyce-Shaikh, B., Blumenschein, W. M., McClanahan, T. K., O'Shea, J. J., & Cua, D. J. (2009) · Nature Immunology · doi:10.1038/ni.1698 · Cited by 1,074
Th17 and regulatory T cells in mediating and restraining inflammation
Littman, D. R., & Rudensky, A. Y. (2010) · Cell · doi:10.1016/j.cell.2010.02.021 · Cited by 1,039
CD4 + Regulatory T Cells Control T H 17 Responses in a Stat3-Dependent Manner
Chaudhry, A., Rudra, D., Treuting, P., Samstein, R. M., Liang, Y., Kas, A., & Rudensky, A. Y. (2009) · Science · doi:10.1126/science.1172702 · Cited by 1,000
Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses
Zheng, Y., Chaudhry, A., Kas, A., deRoos, P., Kim, J. M., Chu, T.-T., Corcoran, L., Treuting, P., Klein, U., & Rudensky, A. Y. (2009) · Nature · doi:10.1038/nature07674 · Cited by 958
Cutting Edge: Cure of Colitis by CD4+CD25+ Regulatory T Cells
Mottet, C., Uhlig, H. H., & Powrie, F. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.3939 · Cited by 928
Deacetylase inhibition promotes the generation and function of regulatory T cells
Tao, R. N., de Zoeten, E. F., Özkaynak, E., Chen, C., Wang, L., Porrett, P. M., Li, B., Turka, L. A., Olson, E. N., Greene, M. I., et al. (2007) · Nature Medicine · doi:10.1038/nm1652 · Cited by 927
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR
Sauer, S., Bruno, L., Hertweck, A., Finlay, D. K., Leleu, M., Spivakov, M., Knight, Z. A., Cobb, B. S., Cantrell, D. A., O’Connor, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800928105 · Cited by 888
A protective function for interleukin 17A in T cell–mediated intestinal inflammation
O'Connor Jr, W., Kamanaka, M., Booth, C. J., Town, T., Nakae, S., Iwakura, Y., Kolls, J. K., & Flavell, R. A. (2009) · Nature Immunology · doi:10.1038/ni.1736 · Cited by 756
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis
Karhausen, J., Furuta, G. T., Tomaszewski, J. E., Johnson, R. S., Colgan, S. P., & Haase, V. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421086 · Cited by 655
Self-citationCretney, E., Xin, A., Shi, W., Minnich, M., Masson, F., Miasari, M., Belz, G. T., Smyth, G. K., Busslinger, M., Nutt, S. L., et al. (2011) · Nature Immunology · doi:10.1038/ni.2006 · Cited by 605
Control of Regulatory T Cell Lineage Commitment and Maintenance
Josefowicz, S. Z., & Rudensky, A. Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.009 · Cited by 584
Oldenhove, G., Bouladoux, N. J., Wohlfert, E. A., Hall, J. A., Chou, D. B., dos Santos, L. M., O’Brien, S., Blank, R. B., Lamb, E. W., Natarajan, S., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.10.001 · Cited by 578
GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
Wohlfert, E. A., Grainger, J. R., Bouladoux, N., Konkel, J. E., Oldenhove, G., Ribeiro, C. H., Hall, J. A., Yagi, R., Naik, S., Bhairavabhotla, R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57456 · Cited by 556
Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors
Sitkovsky, M., & Lukashev, D. (2005) · Nature Reviews Immunology · doi:10.1038/nri1685 · Cited by 518
Zarek, P. E., Huang, C.-T., Lutz, E. R., Kowalski, J., Horton, M. R., Linden, J. M., Drake, C. G., & Powell, J. D. (2007) · Blood · doi:10.1182/blood-2007-03-081646 · Cited by 516
JAM-A regulates permeability and inflammation in the intestine in vivo
Laukoetter, M. G., Nava, P., Lee, W. Y., Severson, E. A., Capaldo, C., Babbin, B. A., Williams, I. R., Koval, M. H., Peatman, E., Campbell, J. A., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20071416 · Cited by 512
Coordinated Adenine Nucleotide Phosphohydrolysis and Nucleoside Signaling in Posthypoxic Endothelium
Eltzschig, H. K., Ibla, J. C., Furuta, G. T., Leonard, M. O., Jacobson, K. A., Enjyoji, K., Robson, S. C., & Colgan, S. P. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030891 · Cited by 499
Self-citationAn Essential Role of the Transcription Factor GATA-3 for the Function of Regulatory T Cells
Wang, Y., Su, M. A., & Wan, Y. Y. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.012 · Cited by 461
Metabolic Shifts in Immunity and Inflammation
Kominsky, D. J., Campbell, E. L., & Colgan, S. P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903002 · Cited by 422
Self-citationCaldwell, C. C., Kojima, H., Lukashev, D., Armstrong, J., Farber, M., Apasov, S. G., & Sitkovsky, M. V. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6140 · Cited by 420
Hypoxia-Inducible Factor-1 Is Central to Cardioprotection
Eckle, T. D. L. G., Köhler, D., Lehmann, R., Kasmi, K. C. E., & Eltzschig, H. K. (2008) · Circulation · doi:10.1161/circulationaha.107.758516 · Cited by 410
Self-citationThe Hydroxylase Inhibitor Dimethyloxalylglycine Is Protective in a Murine Model of Colitis
Cummins, E. P., Seeballuck, F., Keely, S. J., Mangan, N. E., Callanan, J. J., Fallon, P. G., & Taylor, C. T. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.10.012 · Cited by 407 · cited 3×
“Particularly during inflammatory hypoxia, HIF-dependent transcription can activate multiple anti-inflammatory mechanisms (13, 14, 22, 48).”
BackgroundHypoxia-inducible factor–dependent induction of netrin-1 dampens inflammation caused by hypoxia
Rosenberger, P., Schwab, J. M., Mirakaj, V., Masekowsky, E., Mager, A., Morote–Garcia, J. C., Unertl, K. E., & Eltzschig, H. K. (2009) · Nature Immunology · doi:10.1038/ni.1683 · Cited by 406
Self-citationSather, B. D., Treuting, P. R., Perdue, N., Miazgowicz, M. M., Fontenot, J. D., Rudensky, A. Y., & Campbell, D. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070081 · Cited by 406
Molecular Mechanisms Underlying FOXP3 Induction in Human T Cells
Mantel, P., Ouaked, N., Rückert, B., Karagiannidis, C., Welz, R., Blaser, K., & Schmidt‐Weber, C. B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.6.3593 · Cited by 405
Epigenetic mechanisms of regulation of Foxp3 expression
Lal, G., & Bromberg, J. S. (2009) · Blood · doi:10.1182/blood-2009-05-219584 · Cited by 382
Cronstein, B. N., Daguma, L., Nichols, D., Hutchison, A. J., & Williams, M. J. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114547 · Cited by 376
Mucosal Protection by Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibition
Robinson, A., Keely, S., Karhausen, J., Gerich, M. E., Furuta, G. T., & Colgan, S. P. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.09.033 · Cited by 368
Self-citationInhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD
Bernhardt, W. M., Wiesener, M. S., Scigalla, P., Chou, J., Schmieder, R. E., Günzler, V., & Eckardt, K.-U. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010010116 · Cited by 340
McMahon, S., Charbonneau, M., Grandmont, S., Richard, D. E., & Dubois, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604507200 · Cited by 335
Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease
Fraisl, P., Aragonés, J., & Carmeliet, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2761 · Cited by 326
Semenza, G. L. (2009) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.69 · Cited by 324
Safran, M., Kim, W. Y., O'Connell, F., Flippin, L., Günzler, V., Horner, J. W., DePinho, R. A., & Kaelin, W. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509459103 · Cited by 305
Tuning Microenvironments: Induction of Regulatory T Cells by Dendritic Cells
Belkaid, Y., & Oldenhove, G. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.005 · Cited by 278
The Th17 immune response is controlled by the Rel–RORγ–RORγT transcriptional axis
Ruan, Q., Kameswaran, V., Zhang, Y., Zheng, S. J., Sun, J., Wang, J., DeVirgiliis, J., Liou, H., Beg, A. A., & Chen, Y. H. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110462 · Cited by 264
Hypoxia controls CD4+CD25+ regulatory T‐cell homeostasis via hypoxia‐inducible factor‐1α
Ben‐Shoshan, J., Maysel-Auslender, S., Mor, A., Keren, G., & George, J. (2008) · European Journal of Immunology · doi:10.1002/eji.200838318 · Cited by 260
Synovial tissue hypoxia and inflammation in vivo
Ng, C. T., Biniecka, M., Kennedy, A., McCormick, J. B., FitzGerald, O., Bresnihan, B., Buggy, D. J., Taylor, C. T., O'Sullivan, J. N., Fearon, U., et al. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.119776 · Cited by 257
Regulatory T Cells Dynamically Control the Primary Immune Response to Foreign Antigen
Haribhai, D., Lin, W. X., Relland, L. M., Truong, N., Williams, C. B., & Chatila, T. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.2961 · Cited by 244
Hypoxia Upregulates the Synthesis of TGF-β1 by Human Dermal Fibroblasts
Falanga, V., Qian, V. S. W., Danielpour, D., Katz, M. H., Roberts, A. B., & Sporn, M. B. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12483126 · Cited by 231
Bour‐Jordan, H., & Bluestone, J. A. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00775.x · Cited by 229
The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia
Grenz, A., Oßwald, H., Eckle, T. D. L. G., Yang, D., Zhang, H., Tran, Z. V., Klingel, K., Ravid, K., & Eltzschig, H. K. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050137 · Cited by 216
Self-citationHIF-1–dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak
Morote–Garcia, J. C., Rosenberger, P., Kuhlicke, J., & Eltzschig, H. K. (2008) · Blood · doi:10.1182/blood-2007-11-126763 · Cited by 211
Self-citationLukashev, D., Klebanov, B., Kojima, H., Grinberg, A., Ohta, A., Berenfeld, L., Wenger, R. H., Ohta, A., & Sitkovsky, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.8.4962 · Cited by 208
T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response
Sitkovsky, M. V. (2009) · Trends in Immunology · doi:10.1016/j.it.2008.12.002 · Cited by 192
Morote–Garcia, J. C., Rosenberger, P., Nivillac, N. M. I., Coe, I. R., & Eltzschig, H. K. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.10.037 · Cited by 183
Self-citationThe role of the transcription factor Foxp3 in the development of regulatory T cells
Kim, J. M., & Rudensky, A. Y. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00426.x · Cited by 181
Thiel, M., Caldwell, C. C., Kreth, S., Kuboki, S., Chen, P., Smith, P., Ohta, A., Lentsch, A. B., Lukashev, D., & Sitkovsky, M. V. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000853 · Cited by 175
McMahon, S., Grondin, F., McDonald, P. P., Richard, D. E., & Dubois, C. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413248200 · Cited by 170
The resurgence of A2B adenosine receptor signaling
Aherne, C. M., Kewley, E. M., & Eltzschig, H. K. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.05.016 · Cited by 162
Self-citationNakamura, H., Makino, Y., Okamoto, K., Poellinger, L., Ohnuma, K., Morimoto, C., & Tanaka, H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7592 · Cited by 158
Hypoxia inducible factor 1α regulates T cell receptor signal transduction
Neumann, A. K., Yang, J., Biju, M. P., Joseph, S. K., Johnson, R. S., Haase, V. H., Freedman, B. D., & Turka, L. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506070102 · Cited by 120
Darce, J. R., Rudra, D., Li, L., Nishio, J., Cipolletta, D., Rudensky, A. Y., Mathis, D. J., & Benoist, C. O. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.007 · Cited by 113
Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes
Biju, M. P., Neumann, A. K., Bensinger, S. J., Johnson, R. S., Turka, L. A., & Haase, V. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9038-9047.2004 · Cited by 111
Molecular mechanisms regulating TGF-β-induced Foxp3 expression
Xu, L., Kitani, A., & Strober, W. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.7 · Cited by 106
Stefanidakis, M., Newton, G. A., Lee, W. Y., Parkos, C. A., & Luscinskas, F. W. (2008) · Blood · doi:10.1182/blood-2008-01-134429 · Cited by 99
Lukashev, D. E., Caldwell, C. C., Ohta, A., Chen, P., & Sitkovsky, M. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104782200 · Cited by 97
Arsenault, D., Lucien, F., & Dubois, C. M. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22792 · Cited by 38
Research works printed but not linked: 3
- 10.1056/NEJMra0910283 · DOI · Paper page
- 10.1084/jem.20110278 · DOI · Paper page
- 10.1016/j.cell.2011.07.033 · DOI · Paper page
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“Hypoxic zones in tumors attract immunosuppressive cells such as myeloidderived suppressor cells (MDSCs; Corzo et al., 2010), tumor-associated macrophages (TAMs; Doedens et al., 2010; Imtiyaz et al., 2010), and regulatory T cells (T reg cells; Clambey et al., 2012).”
BackgroundFueling Immunity: Insights into Metabolism and Lymphocyte Function
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BackgroundHIF transcription factors, inflammation, and immunity
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BackgroundThe hypoxic tumour microenvironment
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Metadata
- Authors
- Clambey, E. T., McNamee, E. N., Westrich, J. A., Glover, L. E., Campbell, E. L., Jedlicka, P., de Zoeten, E. F., Cambier, J. C., Stenmark, K. R., Colgan, S. P., & Eltzschig, H. K.
- Affiliations
- Mucosal Inflammation Program,
- Department of Anesthesiology, Departments of bMedicine,
- Pathology, and
- Pediatrics and Genetics (US)
- Integrated Department of Immunology, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-17
- Volume
- 109
- Issue
- 41
- Pages
- E2784-93
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3478644
- OpenAlex
- W1986925527
- Cited by
- 560
- References
- 71
- Citations by year
- 2026: 28 · 2025: 31 · 2024: 35 · 2023: 43 · 2022: 60 · 2021: 49 · 2020: 62 · 2019: 44 · 2018: 39 · 2017: 35 · 2016: 38 · 2015: 35 · 2014: 34 · 2013: 25 · 2012: 2
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Maynooth University ePrints and eTheses Archive (Maynooth University) (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL60569, R01HL060569, R01HL098294, R01HL092188, R01‑HL0921)
- National Institute of Diabetes and Digestive and Kidney Diseases (R0-1 DK50189, R01DK050189, R37DK050189, R01DK083385, R01DK095491)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- hypoxia-inducible factor-1α, Foxp3, regulatory T cells, mucosal inflammation, T cell differentiation, transcriptional regulation, T cell-mediated colitis, anti-inflammatory mechanism, oxygen availability
- MeSH terms
- Animals, Hypoxia, Cells, Cultured, Colitis, Female, Flow Cytometry, Gene Expression Regulation, Humans, Inflammation, Interleukin-1, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mice, Transgenic, Cell Hypoxia, Transforming Growth Factor beta, Mice, Knockout, Jurkat Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Cell Proliferation, T-Lymphocytes, Regulatory, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Forkhead Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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