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A critical role for the autophagy gene Atg5 in T cell survival and proliferation
Open accessAbstract
Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5−/− chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5−/− CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5−/− CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
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“In this respect it is noteworthy that some cell-types of the immune system such as dendritic cells 260 seem to tolerate loss of autophagy fairly well, whereas others such as T and B cells are compromised in their development and function after autophagy inhibition.757,758”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [757]
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“Proper induction of autophagy has been shown to be important for the maintenance of cellular bioenergetics and sustained T cell viability after activation (25, 26).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [26]
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Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation
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BackgroundRoles of Autophagy and Autophagy-Related Proteins in Antifungal Immunity
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The role of autophagy in the pathogenesis of systemic lupus erythematosus
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Modulation of the immunity and inflammation by autophagy
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Autophagy and Autophagy-Related Proteins in CNS Autoimmunity
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“In contrast to what Pua and colleagues had reported previously (206), another study described how CD8+ cells downregulate autophagic activity upon activation and during proliferation.”
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Autophagy regulation as a promising approach for improving cancer immunotherapy
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“Its importance extends to the late stages of mammalian embryonic and postnatal development, including neurogenesis, cardiogenesis, hematopoiesis, osteogenesis and folliculogenesis (Choi et al., 2010; Fimia et al., 2007; Nakai et al., 2007; Pua et al., 2007; Settembre et al., 2008).”
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“As indicated by observations in a knockout mouse model, ATG5 a molecule involved in autophagosome formation, is important for T-cell survival and proliferation.(40) The specific deletion of Atg5 in the B lineage demonstrates a role of autophagy in the pro- to pre-B cell transition in the bone marrow and in the mainten…”
BackgroundWei, C.-W., Lee, C.-Y., Lee, D.-J., Chu, C.-F., Wang, J.-C., Wang, T.-C., Jane, W., Chang, Z.-F., Leu, C.-M., Dzhagalov, I. L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.077 · Cited by 36
“In this aspect, it is interesting that autophagydeficient mice, such asCD4-Cre x Atg5f/fmice, also have normal T cell development but greatly increased apoptosis of mature T cells (Pua et al., 2007).”
BackgroundSelf-citationAtg1 allows second-signaled autophagic cell death in Dictyostelium
Luciani, M.-F., Giusti, C., Harms, B., Oshima, Y., Kikuchi, H., Kubohara, Y., & Golstein, P. (2011) · Autophagy · doi:10.4161/auto.7.5.14957 · Cited by 35
Targeting the autophagy pathway for cancer chemoprevention
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“For example, autophagy is critical for normal T and B cell development[41, 42], B cell receptor (BCR) signaling and co-stimulation[43], macrophage function[44], apoptotic cell clearance[45], and antimicrobial function of Paneth cells[46] in the small intestine.”
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Goletti, D., Petruccioli, E., Romagnoli, A., Piacentini, M., & Fimia, G. M. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.01.002 · Cited by 35
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A Cytosolic Phospholipase A2-Initiated Lipid Mediator Pathway Induces Autophagy in Macrophages
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“Elevated ROS production is thought to be an important link between autophagy and apoptosis and the reduction in peripheral T cell number has been attributed to the pro-survival effects of autophagy [57, 59].”
BackgroundAutophagy in Plasma Cell Pathophysiology
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“In following studies, the development of mature T cells was found to require an active negative control on the intracellular production of reactive oxygen species, which in turn relies on efficient mitophagy (55, 57).”
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“In the absence of the autophagy protein Atg5, both CD4 and CD8 T lymphocytes fail to undergo efficient proliferation and rapidly undergo apoptosis in the peripheral lymphoid organs (40).”
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“liferate even on stimulation of TCR (5).”
Rajput, M., Abdelsalam, K. W., Darweesh, M. F., Braun, L. J., Kerkvliet, J. G., Hoppe, A. D., & Chase, C. C. L. (2017) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2017.09.006 · Cited by 33
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“Naive T cells are dependent on autophagy 1,5 ; to understand why, we used mass spectrometry to quantitatively analyze how autophagy shapes naive T cell proteomes.”
InfluentialTherapy-induced microenvironmental changes in cancer
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“volved in the survival and differentiation of T cells, monocytes, and macrophages [127–130] and plays a role in immune cell migration by enhancing β1 integrin recycling and reduc-”
BackgroundNewly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress
Zhang, S., Zhang, X., Wang, K., Xu, X., Li, M., Zhang, J., Zhang, Y., Hao, J., Sun, X., Chen, Y., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700721 · Cited by 32
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“Alam’s research indicates that integrin molecules can bind to different extracellular matrix (ECM) molecules due to overlapping affinities [10].”
BackgroundJeong, J., Choi, Y. J., & Lee, H. K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.860146 · Cited by 33
“Several studies have reported enlarged ER and mitochondria in autophagy-deficient murine CD4+ T cells, including Atg7, Atg5, and Atg3 (Pua et al., 2009; Stephenson et al., 2009; Jia and He, 2011).”
BackgroundResultInfluentialTang, L., Zhang, H., Zhou, F., Wei, Q., Du, M., Wu, J., Li, C., Luo, W., Zhou, J., Wang, X., et al. (2024) · 癌症：英文版 · doi:10.1002/cac2.12525 · Cited by 33
“Multiple stress signals affect the autophagy-dependent changes in various immune cells, including NK cells, T cells, regulatory T cells and antigen-processing cells (APCs), and could also directly regulate anti-tumor immunity [59–61].”
BackgroundHarnessing Autophagic Network Is Essential for Trophoblast Stem Cell Differentiation
Chakraborty, S., Bose, R., Islam, S., Das, S., & Ain, R. (2020) · Stem Cells and Development · doi:10.1089/scd.2019.0296 · Cited by 31
“Previous reports provide evidence about the role of autophagy during differentiation of erythrocytes [31], lymphocytes [32,33], adipocytes [34], hepatocytes [35], neurons [36], and so on.”
Autophagy in T‐cell differentiation, survival and memory
Wang, L., Das, J. K., Kumar, A., Peng, H., Ren, Y., Xiong, X., Yang, J., & Song, J. J. (2020) · Immunology and Cell Biology · doi:10.1111/imcb.12422 · Cited by 31
“proliferate following TCR stimulation, suggesting a critical role for autophagy in determining the survival of T cells in the peripheral organs of the host.(43) In a mouse model, it has been shown that T cell survival is closely related to mitochondrial function and reactive oxygen species (ROS) regulated by autophagy.”
BackgroundCan Probiotics Emerge as Effective Therapeutic Agents in Apical Periodontitis? A Review
Kumar, G., Tewari, S., Tagg, J. R., Chikindas, M. L., Popov, I. V., & Tiwari, S. K. (2021) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-021-09750-2 · Cited by 31
REDD1 Is Essential for Optimal T Cell Proliferation and Survival
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“In fact, T cells unable to undergo autophagy due to genetic deletion of the Atg5 gene present a remarkably similar phenotype to REDD1 deficient T cells [39].”
BackgroundAutophagy mediates oral submucous fibrosis
Jiang, L., Zhao, T., ZHANG, P., Xu, C., RONG, Z.-X., YAN, Z.-Y., & Fang, C. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3145 · Cited by 32
“Furthermore, mice with neuron‑specific Atg5 or Atg7 knockout suffer from neurodegeneration and apoptotic neuronal death, and T‑cell‑specific Atg5 deficiency leads to an increase in the peripheral T-cell apoptosis upon T-cell activation (37-39).”
Mechanisms regulating immune surveillance of cellular stress in cancer
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“In immune cells, autophagy can promote proliferation, antigen presentation, cell activation and cytokine secretion [74, 133, 177].”
BackgroundThe nonautophagic functions of autophagy-related proteins
Shang, J.-N., Yu, C.-G., Li, R. Q., Xi, Y., Jian, Y. J., Xu, N., & Chen, S. (2023) · Autophagy · doi:10.1080/15548627.2023.2254664 · Cited by 30
“Moreover, Pua et al. showed that ATG5 May regulate T-cell proliferation independent of its autophagic function [106].”
BackgroundMacroautophagy in T Lymphocyte Development and Function
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“AUTOPHAGY INDUCTION IN T LYMPHOCYTES Although relatively low, autophagy can be detected in all subsets of thymocytes and freshly isolated naïve T lymphocytes (Li et al., 2006; Pua et al., 2007; Stephenson et al., 2009).”
BackgroundSelf-citationTang, Z., Zhang, Z., Zhang, H., Wang, Y., Zhang, Y., Zhao, J.-H., Yang, H., & Wang, Z. (2019) · Cells · doi:10.3390/cells9010071 · Cited by 31
“The induction of autophagy is highly regulated, of which the role is tightly associated with many aspects of cell activities, such as cell proliferation [2], metabolism [3], and hormone production [4].”
BackgroundThe crosslinks between ferroptosis and autophagy in asthma
Lv, X., Tang, W., Qin, J., Wang, W., Dong, J., & Wei, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1140791 · Cited by 33
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Yousefi, S., & Simon, H. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.12.023 · Cited by 32
“Interestingly, Atg5 is also required for efficient T cell proliferation [38].”
BackgroundSickness-Associated Anorexia: Mother Nature’s Idea of Immunonutrition?
van Niekerk, G., Isaacs, A. W., Nell, T. A., & Engelbrecht, A. (2016) · Mediators of Inflammation · doi:10.1155/2016/8071539 · Cited by 32
“Previous studies [117, 118] have identified an early upregulation of autophagy in proliferating T cells.”
BackgroundA critical role for the autophagy gene Atg5 in T cell survival and proliferation
Pua, H. H., Dzhagalov, I. L., Chuck, M. I., Mizushima, N., & He, Y.-W. (2007) · The Journal of Cell Biology · doi:10.1083/jcb1761oia5 · Cited by 30
Self-citationAn old problem with new solutions: Strategies to improve vaccine efficacy in the elderly
Bell, M. R., & Kutzler, M. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114175 · Cited by 29
Amyloid β Peptides Promote Autophagy-Dependent Differentiation of Mouse Neural Stem Cells
Fonseca, M. B., Solá, S., Xavier, J. M., Dionísio, P. A., & Rodrigues, C. M. P. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8471-1 · Cited by 30
“Autophagy, as a dynamic process of protein degradation, fulfills multiple functions in mammalian cells and is essential for cellular survival and differentiation, development, and homeostasis [15–20].”
Caught in the cROSsfire: GSH Controls T Cell Metabolic Reprogramming
Geltink, R. I. K., O’Sullivan, D., & Pearce, E. L. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.022 · Cited by 29
“The lack of cell death until 48 hr after activation in the absence of GCLC revealed that these cells remain viable, which could be achieved by engaging autophagy (Pua et al., 2007).”
BackgroundZFP91 is required for the maintenance of regulatory T cell homeostasis and function
Wang, A., Ding, L., Wu, Z., Ding, R., Teng, X.-L., Wang, F., Hu, Z., Chen, L., Yu, X., & Zou, Q. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201217 · Cited by 28
“Autophagy is induced after TCR and cytokine stimulation to promote conventional T cell proliferation and survival (Hubbard et al., 2010; Li et al., 2006; Pua et al., 2007).”
BackgroundWei, H., Li, L., Zhang, H., Xu, F., Chen, L.-Q., Che, G., & Wang, Y. (2021) · Cell Cycle · doi:10.1080/15384101.2020.1867780 · Cited by 28
“ATG5, a member of autophagy-related genes, was confirmed to affect cell survival through regulating autophagy [34].”
BackgroundThe Presence of Autophagy in Human Periapical Lesions
Zhu, L., Yang, J., Zhang, J., & Peng, B. (2013) · Journal of Endodontics · doi:10.1016/j.joen.2013.07.013 · Cited by 27
Apoptosis and autophagy in the regulation of T lymphocyte function
Dunkle, A. D., & He, Y.-W. (2010) · Immunologic Research · doi:10.1007/s12026-010-8195-5 · Cited by 28
“In contrast, the numbers of CD4 and CD8 T cells were severely reduced in the peripheral compartments of Atg5 chimeric mice [117].”
BackgroundMethodInfluentialSelf-citationKim, J. H., Yu, D.-H., Kim, H., Huh, Y. H., Cho, S., Lee, J.-K., Kim, H., & Kim, H. R. (2017) · Toxicology and Industrial Health · doi:10.1177/0748233717740066 · Cited by 28
Mitofusin 2 Promotes Apoptosis of CD4 + T Cells by Inhibiting Autophagy in Sepsis
Lan, Y., Zhao, G., Wu, Y., Ke, H.-L., Hong, G., Zhang, H., Dong, N., Wu, Y., Yao, Y.-M., & Lu, Z. (2017) · Mediators of Inflammation · doi:10.1155/2017/4926205 · Cited by 28
“Moreover, studies have established that autophagy plays a key role in T cells [20, 21].”
BackgroundFuller, A. M., Pruitt, H. C., Liu, Y., Irizarry-Negron, V. M., Pan, H., Song, H., Devine, A., Katti, R., Devalaraja, S., Ciotti, G. E., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci167826 · Cited by 26
“Autophagy is rapidly induced upon T cell activation, and the essential autophagy genes Atg5 and Atg7 are critical for mature T cell survival, activation, and expansion (69, 70).”
Modulation of Pathogen Recognition by Autophagy
Oh, J. E., & Lee, H. K. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00044 · Cited by 28
“2007; Pua et al., 2007; Miller et al., 2008).”
The Complex Link between Apoptosis and Autophagy: a Promising New Role for RB
Delou, J. M. D. A., Biasoli, D., & Borges, H. L. (2016) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201620160127 · Cited by 28
Autophagy in the Vertebrate Inner Ear
Magariños, M., Pulido, S., Aburto, M. R., de Iriarte, R., & Varela‐Nieto, I. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00056 · Cited by 28
“Atg5 and Atg7 deficiency is associated with a reduction in thymocytes and B-lymphocytes (Pua et al., 2007), as well as reduced levels of adipocyte differentiation factors and decreased lipid adipose mass (Singh et al., 2009).”
BackgroundAnti-tumor immunity influences cancer cell reliance upon ATG7
Arensman, M. D., Yang, X. S., Zhong, W., Bisulco, S., Upeslacis, E., Rosfjord, E. C., Deng, S., Abraham, R. T., & Eng, C. H. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1800162 · Cited by 27
Autophagy and Lymphocyte Homeostasis
Pua, H. H., & He, Y.-W. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-00302-8_4 · Cited by 28
Self-citationPascall, J. C., Rotondo, S., Mukadam, A. S., Oxley, D., Webster, J. A., Walker, S. A., Piron, J., Carter, C., Ktistakis, N. T., & Butcher, G. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077782 · Cited by 27
“In both cases, intrathymic T cell development is relatively normal while the peripheral T cell population is severely depleted and the remaining T cells [47,48] are unusual in phenotype, with marked absence of resting, naïve T cells [49].”
BackgroundZinc finger protein Zfp335 is required for the formation of the naïve T cell compartment
Han, Y., Wu, S., Foo, C.-S., Horton, R. M., Jenne, C. N., Watson, S. R., Whittle, B., Goodnow, C. C., & Cyster, J. G. (2014) · eLife · doi:10.7554/elife.03549 · Cited by 25
“A small number of studies have shown that autophagy plays a role in mature T cell survival (Pua et al., 2007; He et al., 2012; Parekh et al., 2013), possibly by ensuring the clearance of excess mitochondria Genes and chromosomes | Immunology Research article Genes and chromosomes | Immunology Han…”
BackgroundDown-regulation of ASIC1 suppressed gastric cancer via inhibiting autophagy
Zhang, Q., Wu, S., Zhu, J., Chai, D., & Gan, H. (2017) · Gene · doi:10.1016/j.gene.2017.01.014 · Cited by 27
Regulation of eosinophil functions by autophagy
Germič, N., Hosseini, A., Yousefi, S., Karaulov, A. V., & Simon, H. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-021-00860-1 · Cited by 26
Interactions of Autophagy and the Immune System in Health and Diseases
Pant, A., Yao, X., Lavedrine, A., Viret, C., Dockterman, J., Chauhan, S. C., Shi, C.-S., Manjithaya, R. R., Cadwell, K., Kufer, T. A., et al. (2022) · Autophagy Reports · doi:10.1080/27694127.2022.2119743 · Cited by 28
Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis
Afzal, S., Hao, Z., Itsumi, M., Abouelkheer, Y., Brenner, D., Gao, Y., Wakeham, A. C., Hong, C., Li, W. Y., Sylvester, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423588112 · Cited by 26
“To determine whether UVRAG is necessary for the prominent autophagosome formation induced upon T-cell activation (1, 19), we cultured UR and UR;Lck-Cre naïve peripheral T cells in complete medium, or in medium containing anti-CD3 plus anti-CD28 Abs, with or without the autophagy inhibitor chloroquine (CQ).”
BackgroundMethodAutophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients
Paunović, V., Vuković, I., Milenkovic, M. M., Janjetović, K., Pravica, V., Dujmović, I., Milošević, E., Martinović, V., Mesaroš, Š., Drulovic, J. S., et al. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.03.001 · Cited by 26
Autophagy in regulatory T cells: A double-edged sword in disease settings
Zhang, J., Chen, L., Xiong, F., Zhang, S., Huang, K., Zhang, Z., & Wang, C. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.02.004 · Cited by 27
Autophagy preserves hematopoietic stem cells by restraining MTORC1-mediated cellular anabolism
Borsa, M., Obba, S., Richter, F. C., Zhang, H., Riffelmacher, T., Carrelha, J., Alsaleh, G., Jacobsen, S. E. W., & Simon, A. K. (2023) · Autophagy · doi:10.1080/15548627.2023.2247310 · Cited by 27
“As loss of autophagy also results in extensive depletion of most mature blood cell lineages such as erythrocytes [21], platelets [22], and T cells [23], leading to cytopenia in the periphery, HSCs and their progenitors will be activated to replenish these lineages.”
BackgroundKerins, M. J., Liu, P., Tian, W., Mannheim, W., Zhang, D. D., & Ooi, A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00037-19 · Cited by 25
Chen, X., Wang, L., Deng, Y., Li, X., Li, G., Zhou, J. W., Cheng, D., Yang, Y., Yang, Q., Chen, G., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01356 · Cited by 24
“Additionally, previous studies have implied that knockout of Atg5 or Vps34, two key autophagy-related factors, significantly inhibited the proliferation of T cells T cells following TCR triggering (14).”
BackgroundHydroxychloroquine inhibits the mitochondrial antioxidant system in activated T cells
Kim, M. L., Hardy, M. Y., Edgington‐Mitchell, L. E., Ramarathinam, S. H., Chung, S. Z., Russell, A. K., Currie, I., Sleebs, B. E., Purcell, A. W., Tye–Din, J. A., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103509 · Cited by 27
GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans
Yao, Y., Jiang, P. D., Chao, B. N., Cağdaş, D. N., Kubo, S., Balasubramaniyam, A., Zhang, Y., Shadur, B., NaserEddin, A., Folio, L. R., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20201405 · Cited by 23
Wang, Y., Jin, X., Li, M., Gao, J., Zhao, X., Ma, J., Shi, C., He, B., Hu, L., Shi, J., et al. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.2c09024 · Cited by 25
Li, K., Wei, X., Li, K., Zhang, Q., Zhang, J., Wang, D., & Yang, J. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04865-x · Cited by 23
“For example, in mouse, the dysfunctional or defective autophagy resulting from inhibitor administration or gene knockout impaired the differentiation of Th1, Th17, and Treg cells [49–51]; weakened the CD8+ effector T cell response during influenza infection [48]; and aggravated the apoptosis of CD4+ T cells and failed…”
BackgroundThe Role of Autophagy and Apoptosis During Embryo Development
Agnello, M., Bosco, L., Chiarelli, R., Martino, C., & Roccheri, M. C. (2015) · InTech eBooks · doi:10.5772/61765 · Cited by 27
Autophagy as a pathogenic mechanism and drug target in lymphoproliferative disorders
Pierdominici, M., Barbati, C., Vomero, M., Locatelli, S. L., Carlo‐Stella, C., Ortona, E., & Malorni, W. (2013) · The FASEB Journal · doi:10.1096/fj.13-235655 · Cited by 24
“Autophagosomes can be detected within freshly primary murine T lymphocytes, and their number and size increase on withdrawal of serum, amino acids, or TCR stimulation (23, 28, 29).”
BackgroundTargeting autophagy in thyroid cancers
Wei, W., Hardin, H. A., & Luo, Q. (2019) · Endocrine Related Cancer · doi:10.1530/erc-18-0502 · Cited by 25
Finetti, F., Cassioli, C., Cianfanelli, V., Zevolini, F., Onnis, A., Gesualdo, M., Brunetti, J., Cecconi, F., & Baldari, C. T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634003 · Cited by 24
“Basal autophagy is one of the main mechanisms that underlie this extended T cell survival (Kovacs et al., 2012; Pua et al., 2007; Xu et al., 2014).”
BackgroundPharmacological insights into autophagy modulation in autoimmune diseases
Wu, M.-Y., Wang, E., Feng, D., Li, M., Ye, R. D., & Lu, J. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.026 · Cited by 24
The Role of Autophagy in Salivary Gland Homeostasis and Stress Responses
Morgan-Bathke, M. E., Lin, H. H., Ann, D. K., & Limesand, K. H. (2015) · Journal of Dental Research · doi:10.1177/0022034515590796 · Cited by 23
Autophagy and Mechanisms of Effective Immunity
Mintern, J. D., & Villadangos, J. A. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00060 · Cited by 25
“The proliferative defect is not rescued by anti-CD28 or IL-2 and the cells display normal levels of TCR and upregulate T cell activation markers CD69 and CD25.”
BackgroundInfluentialZhang, L., Ai, Y., & Tsung, A. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3071 · Cited by 23
“Atg5 deficient CD4 + and CD8 + T cells failed to repopulate the periphery due to high levels of cell death and failure to undergo efficient proliferation following T cell receptor stimulation (64).”
Metadata
- Authors
- Pua, H. H., Dzhagalov, I., Chuck, M., Mizushima, N., & He, Y.-W.
- Affiliations
- Duke Medical Center (US)
- Japan Science and Technology Agency (JP)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-12-26
- Volume
- 204
- Issue
- 1
- Pages
- 25-31
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118420
- OpenAlex
- W2154663531
- Cited by
- 622
- References
- 29
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 17 · 2023: 23 · 2022: 25 · 2021: 31 · 2020: 34 · 2019: 35 · 2018: 34 · 2017: 39 · 2016: 45 · 2015: 35 · 2014: 34 · 2013: 42 · 2012: 55
- FWCI
- 19.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA092123, CA92123)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK040561)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- autophagy, ATG5, ATG7, T cell proliferation, T cell development, autophagosomes, CD8+ T cells, CD4+ T cells, T cell receptor stimulation, lymphocyte apoptosis, chimeric mice
- MeSH terms
- Autophagy-Related Protein 5, Animals, Autophagy, Base Sequence, Cell Differentiation, Cell Survival, Female, Mice, Inbred C57BL, Microtubule-Associated Proteins, Pregnancy, Receptors, Antigen, T-Cell, T-Lymphocytes, Fetal Tissue Transplantation, DNA Primers, Transplantation Chimera, Mice, Knockout, Hematopoietic Stem Cell Transplantation, CD8-Positive T-Lymphocytes, Cell Proliferation, Mice
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