Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs
Open accessAbstract
Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.
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CD103+ DCs selectively carry apoptotic intestinal epithelial cells to mesenteric lymph nodes, which function as critical determinants to induce tolerogenic CD4+ regulatory T-cell differentiation in mice.
“CD103+ DCs selectively carry apoptotic intestinal epithelial cells to mesenteric lymph nodes, which function as critical determinants to induce tolerogenic CD4+ regulatory T-cell differentiation in mice [161].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [161]
CD24+ DCs generally exert their removal function via T-cell regulation.
“CD24+ DCs generally exert their removal function via T-cell regulation.”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [161]
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Cites
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease
The International IBD Genetics Consortium (IIBDGC), Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P., Hui, K. Y., Lee, J. C., Philip Schumm, L., Sharma, Y., et al. (2012) · Nature · doi:10.1038/nature11582 · Cited by 4,722 · see citing works
Self-citationMonocyte recruitment during infection and inflammation
Shi, C., & Pamer, E. G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3070 · Cited by 3,015 · see citing works
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866 · see citing works
Genetics and pathogenesis of inflammatory bowel disease
Khor, B., Gardet, A., & Xavier, R. J. (2011) · Nature · doi:10.1038/nature10209 · Cited by 2,630 · see citing works
Jung, S., Unutmaz, D., Wong, P., Sano, G., Santos, K. D. L., Sparwasser, T., Wu, S., Vuthoori, S., Ko, K., Zavala, F., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00365-5 · Cited by 1,953 · see citing works
Apoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223 · see citing works
Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176 · see citing works
Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia
Eisenhoffer, G. T., Loftus, P. D., Yoshigi, M., Otsuna, H., Chien, C.-B., Morcos, P. A., & Rosenblatt, J. (2012) · Nature · doi:10.1038/nature10999 · Cited by 876 · see citing works
Origin of the Lamina Propria Dendritic Cell Network
Bogunovic, M., Ginhoux, F., Helft, J., Shang, L., Hashimoto, D., Greter, M., Liu, K., Jakubzick, C., Ingersoll, M. A., Leboeuf, M., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.010 · Cited by 859 · see citing works
Schlitzer, A., McGovern, N. N., Teo, P., Zelante, T., Atarashi, K., Low, D., Ho, A. W. S., See, P., Shin, A., Wasan, P. S., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.011 · Cited by 834 · see citing works
Deciphering the transcriptional network of the dendritic cell lineage
Miller, J. C., Brown, B. D., Shay, T., Gautier, E. L., Jojic, V., Cohain, A. T., Pandey, G. S., Leboeuf, M., Elpek, K. G., Helft, J., et al. (2012) · Nature Immunology · doi:10.1038/ni.2370 · Cited by 779 · see citing works
Madison, B., Dunbar, L., Qiao, X. T., Braunstein, K., Braunstein, E. M., & Gumucio, D. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204935200 · Cited by 748 · see citing works
How Tolerogenic Dendritic Cells Induce Regulatory T Cells
Maldonado, R., & von Andrian, U. H. (2010) · Advances in immunology · doi:10.1016/b978-0-12-380995-7.00004-5 · Cited by 543 · see citing works
Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine
Kim, K. S., Hong, S., Han, D., Yi, J., Jung, J., Yang, B., Lee, J. Y., Lee, M., & Surh, C. D. (2016) · Science · doi:10.1126/science.aac5560 · Cited by 541 · see citing works
Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature
Haberman, Y., Tickle, T. L., Dexheimer, P. J., Kim, M., Tang, D., Karns, R. A., Baldassano, R. N., Noe, J. D., Rosh, J. R., Markowitz, J. F., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75436 · Cited by 521 · see citing works
Diphtheria toxin receptor–mediated conditional and targeted cell ablation in transgenic mice
Saito, M., Iwawaki, T., Taya, C., Yonekawa, H., Noda, M., Inui, Y., Mekada, E., Kimata, Y., Tsuru, A., & Kohno, K. (2001) · Nature Biotechnology · doi:10.1038/90795 · Cited by 512 · see citing works
Ubiquitin signaling in immune responses
Hu, H., & Sun, S. (2016) · Cell Research · doi:10.1038/cr.2016.40 · Cited by 481 · see citing works
Tran, D. Q., Andersson, J., Wang, R., Ramsey, H. E., Unutmaz, D., & Shevach, E. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901944106 · Cited by 473 · see citing works
Spred is a Sprouty-related suppressor of Ras signalling
Wakioka, T., Sasaki, A. T., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., & Yoshimura, A. (2001) · Nature · doi:10.1038/35088082 · Cited by 446 · see citing works
Death in the intestinal epithelium—basic biology and implications for inflammatory bowel disease
Blander, J. M. (2016) · FEBS Journal · doi:10.1111/febs.13771 · Cited by 191 · see citing works
CD205 (DEC-205): A recognition receptor for apoptotic and necrotic self
Shrimpton, R. E., Butler, M., Morel, A., Eren, E., Hue, S. S., & Ritter, M. A. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2008.11.016 · Cited by 187 · see citing works
Intestinal dendritic cells in the regulation of mucosal immunity
Bekiaris, V., Persson, E. K., & Agace, W. W. (2014) · Immunological Reviews · doi:10.1111/imr.12194 · Cited by 158 · see citing works
Arbore, G., & Kemper, C. (2016) · European Journal of Immunology · doi:10.1002/eji.201546131 · Cited by 141 · see citing works
OASL1 inhibits translation of the type I interferon–regulating transcription factor IRF7
Lee, M. S., Kim, B., Oh, G. T., & Kim, Y.-J. (2013) · Nature Immunology · doi:10.1038/ni.2535 · Cited by 139 · see citing works
A long-awaited merger of the pathways mediating host defence and programmed cell death
Blander, J. M. (2014) · Nature reviews. Immunology · doi:10.1038/nri3720 · Cited by 126 · see citing works
Guardians of the Gut – Murine Intestinal Macrophages and Dendritic Cells
Gross, M., Salame, T., & Jung, S. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00254 · Cited by 110 · see citing works
The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice
Bongers, G., Maussang, D., Muniz, L. R., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42563 · Cited by 106 · see citing works
PIKfyve Inhibition Interferes with Phagosome and Endosome Maturation in Macrophages
Kim, G. H. E., Dayam, R. M., Prashar, A., Terebiznik, M. R., & Botelho, R. J. (2014) · Traffic · doi:10.1111/tra.12199 · Cited by 105 · see citing works
Bongers, G., Pacer, M. E., Geraldino, T. H., Chen, L., He, Z., Hashimoto, D., Furtado, G. C., Ochando, J., Kelley, K. A., Clemente, J. C., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131587 · Cited by 78 · see citing works
Guo, Z., Jang, M. H., Otani, K., et al. (2008) · International Immunology · doi:10.1093/intimm/dxm143 · Cited by 48 · see citing works
Cummings, R. J., Gerber, S. A., Judge, J., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201371 · Cited by 29 · see citing works
Guo, X., Li, H., Xu, H., et al. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.04.007 · Cited by 29 · see citing works
Moon, C. M., Shin, D., Son, N., Shin, E., Hong, S. P., Kim, T. I., Kim, W. H., & Cheon, J. H. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12214 · Cited by 15 · see citing works
Fang, W., Douglas, I. S., Wang, C., Kao, H.-C., Chang, Y., Tseng, C., Huang, K., Chang, H., & Lin, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102622 · Cited by 10 · see citing works
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Efferocytosis in health and disease
Doran, A. C., Yurdagul, A., & Tabas, I. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0240-6 · Cited by 1,066 · see citing works
Type 2 immunity in tissue repair and fibrosis
Gieseck, R. L., Wilson, M. S., & Wynn, T. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.90 · Cited by 1,055 · see citing works
Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD
Na, Y. R., Stakenborg, M., Seok, S. H., & Matteoli, G. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0172-4 · Cited by 900 · see citing works
The clearance of dead cells by efferocytosis
Boada-Romero, E., Martinez, J., Heckmann, B. L., & Green, D. R. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0232-1 · Cited by 893 · see citing works
Macrophages in health and disease
Park, M. D., Silvin, A., Ginhoux, F., & Merad, M. (2022) · Cell · doi:10.1016/j.cell.2022.10.007 · Cited by 644 · see citing works
Regulation of inflammation by microbiota interactions with the host
Blander, J. M., Longman, R., Iliev, I. D., Sonnenberg, G. F., & Artis, D. (2017) · Nature Immunology · doi:10.1038/ni.3780 · Cited by 649 · see citing works
Tissue-specific macrophages: how they develop and choreograph tissue biology
Mass, E., Nimmerjahn, F., Kierdorf, K., & Schlitzer, A. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00848-y · Cited by 621 · see citing works
Pathophysiology of Inflammatory Bowel Disease: Innate Immune System
Saéz, Á., Herrero‐Fernández, B., Gómez-Bris, R., Sánchez-Martinez, H., & González, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021526 · Cited by 613 · see citing works
Biological functions of lymphatic vessels
Petrova, T. V., & Koh, G. Y. (2020) · Science · doi:10.1126/science.aax4063 · Cited by 461 · see citing works
Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host
Meisel, M., Hinterleitner, R., Pacis, A., Chen, L., Earley, Z. M., Mayassi, T., Pierre, J. F., Ernest, J. D., Galipeau, H. J., Thuille, N., et al. (2018) · Nature · doi:10.1038/s41586-018-0125-z · Cited by 406 · see citing works
Cell death in the gut epithelium and implications for chronic inflammation
Patankar, J. V., & Becker, C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0326-4 · Cited by 421 · see citing works
Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology
Morioka, S., Maueröder, C., & Ravichandran, K. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.018 · Cited by 391 · see citing works
Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression
Shaw, T. N., Houston, S. A., Wemyss, K., Bridgeman, H. M., Barbera, T. A., Zangerle-Murray, T., Strangward, P., Ridley, A. J. L., Wang, P., Tamoutounour, S., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180019 · Cited by 382 · see citing works
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Guan, F., Wang, R., Yi, Z., Luo, P., Liu, W., Xie, Y., Liu, Z., Xia, Z., Zhang, H., & Cheng, Q. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02124-y · Cited by 371 · see citing works
Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
Morioka, S., Perry, J. S. A., Raymond, M. H., Medina, C. B., Zhu, Y., Zhao, L., Serbulea, V., Önengüt-Gümüşcü, S., Leitinger, N., Kucenas, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0735-5 · Cited by 370 · see citing works
Macrophages in intestinal homeostasis and inflammatory bowel disease
Hegarty, L. M., Jones, G., & Bain, C. C. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00769-0 · Cited by 373 · see citing works
Origin, Differentiation, and Function of Intestinal Macrophages
Bain, C. C., & Schridde, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02733 · Cited by 348 · see citing works
Organ-specific lymphatic vasculature: From development to pathophysiology
Petrova, T. V., & Koh, G. Y. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171868 · Cited by 303 · see citing works
Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease
Mayr, L., Grabherr, F., Schwärzler, J., Reitmeier, I., Sommer, F., Gehmacher, T., Niederreiter, L., He, G.-W., Ruder, B., Kunz, K. T. R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15646-6 · Cited by 292 · see citing works
Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells
Roberts, A. W., Lee, B. L., Deguine, J., John, S., Shlomchik, M. J., & Barton, G. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.10.006 · Cited by 261 · see citing works
Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells
Ruhland, M. K., Roberts, E. W., Cai, E., Mujal, A. M., Marchuk, K., Beppler, C., Nam, D., Serwas, N. K., Binnewies, M., & Krummel, M. F. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.05.002 · Cited by 241 · see citing works
Inflammasomes and adaptive immune responses
Deets, K. A., & Vance, R. E. (2021) · Nature Immunology · doi:10.1038/s41590-021-00869-6 · Cited by 238 · see citing works
Henson, P. M. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125315 · Cited by 208 · see citing works
Macrophage Clearance of Apoptotic Cells: A Critical Assessment
Gordon, S., & Plüddemann, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00127 · Cited by 201 · see citing works
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
Inflammasome, Inflammation, and Tissue Homeostasis
Rathinam, V. A. K., & Chan, F. K.-M. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.01.004 · Cited by 192 · see citing works
Roles of Macrophages in the Development and Treatment of Gut Inflammation
Han, X., Ding, S., Jiang, H., & Liu, G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.625423 · Cited by 187 · see citing works
M2 macrophages in kidney disease: biology, therapies, and perspectives
Chen, T., Cao, Q., Wang, Y., & Harris, D. C. H. (2019) · Kidney International · doi:10.1016/j.kint.2018.10.041 · Cited by 189 · see citing works
Dendritic Cells As Inducers of Peripheral Tolerance
Iberg, C. A., Jones, A., & Hawiger, D. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.07.007 · Cited by 178 · see citing works
Dendritic cell maturation in cancer
Moon, C. Y., Belabed, M., Park, M. D., Mattiuz, R., Puleston, D. J., & Mérad, M. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00787-3 · Cited by 186 · see citing works
Macrophages in the gut: Masters in multitasking
Delfini, M., Stakenborg, N., Viola, M. F., & Boeckxstaens, G. E. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.005 · Cited by 174 · see citing works
Ladinsky, M. S., Araújo, L. P., Zhang, X., Veltri, J., Galán-Díez, M., Soualhi, S., Lee, C., Irie, K., Pinker, E. Y., Narushima, S., et al. (2019) · Science · doi:10.1126/science.aat4042 · Cited by 170 · see citing works
Das, T., Chen, Z., Hendriks, R. W., & Kool, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00104 · Cited by 166 · see citing works
Castro‐Dopico, T., Fleming, A., Dennison, T. W., Ferdinand, J. R., Harcourt, K., Stewart, B. J., Cader, M. Z., Tuong, Z. K., Jing, C., Lok, L. S. C., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107857 · Cited by 159 · see citing works
Plebanek, M. P., Xue, Y., Nguyen, Y.-V., DeVito, N. C., Wang, X., Holtzhausen, A., Beasley, G. M., Theivanthiran, B., & Hanks, B. A. (2024) · Science Immunology · doi:10.1126/sciimmunol.adi4191 · Cited by 164 · see citing works
Macrophages in gastrointestinal homeostasis and inflammation
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Regulation of Innate and Adaptive Immunity by TGFβ
Kelly, A., Houston, S. A., Sherwood, E., Casulli, J., & Travis, M. A. (2017) · Advances in immunology · doi:10.1016/bs.ai.2017.01.001 · Cited by 142 · see citing works
Redefining the Role of Langerhans Cells As Immune Regulators within the Skin
West, H. C., & Bennett, C. L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01941 · Cited by 141 · see citing works
Efferocytosis and Its Role in Inflammatory Disorders
Ge, Y., Huang, M., & Yao, Y.-M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.839248 · Cited by 143 · see citing works
Macrophages Maintain Epithelium Integrity by Limiting Fungal Product Absorption
Chikina, A. S., Nadalin, F., Maurin, M., Jouve, M. J., Thomas-Bonafos, T., Li, X. V., Lameiras, S., Baulande, S., Henri, S., MALISSEN, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.048 · Cited by 138 · see citing works
Abraham, C., Abreu, M. T., & Turner, J. R. (2022) · Gastroenterology · doi:10.1053/j.gastro.2021.12.288 · Cited by 127 · see citing works
T Cell Responses to the Microbiota
Ivanov, I. I., Tuganbaev, T., Skelly, A. N., & Honda, K. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-011829 · Cited by 128 · see citing works
Antigen-specific regulatory T-cell responses to intestinal microbiota
Russler-Germain, E. V., Rengarajan, S., & Hsieh, C.-S. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.65 · Cited by 121 · see citing works
SUMMERS, K. M., Bush, S. J., & Hume, D. A. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000859 · Cited by 111 · see citing works
Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells
Trahtemberg, U., & Mevorach, D. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01356 · Cited by 119 · see citing works
Development, Diversity, and Function of Dendritic Cells in Mouse and HumanPreprint
Anderson, D. A., MURPHY, K. M. M., & Briseño, C. G. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028613 · Cited by 114 · see citing works
LXR signaling controls homeostatic dendritic cell maturation
Bosteels, V., Maréchal, S., Nolf, C. D., Rennen, S., Maelfait, J., Tavernier, S. J., Vetters, J., Velde, E. V. D., Fayazpour, F., Deswarte, K., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.add3955 · Cited by 111 · see citing works
Li, J., Yao, Y.-M., & Tian, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701163 · Cited by 109 · see citing works
Gut macrophages: key players in intestinal immunity and tissue physiology
Muller, P. A., Matheis, F., & Mucida, D. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.11.011 · Cited by 106 · see citing works
Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma
Higuchi, H., Yamakawa, N., Imadome, K., Yahata, T., Kotaki, R., Ogata, J., Kakizaki, M., Fujita, K., Lu, J., Yokoyama, K., et al. (2018) · Blood · doi:10.1182/blood-2017-07-794529 · Cited by 101 · see citing works
Lymphatic vessel: Origin, heterogeneity, biological functions and therapeutic targets
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Desalegn, G., & Pabst, O. (2019) · Nature Communications · doi:10.1038/s41467-019-11148-2 · Cited by 98 · see citing works
Wu, M.-Y., Liu, L., Wang, E., Xiao, H., Cai, C.-Z., Wang, J., Su, H., Wang, Y., Tan, J., Zhang, Z., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1741332 · Cited by 95 · see citing works
Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
Liebold, I., Al Jawazneh, A., Casar, C., Lanzloth, C., Leyk, S., Hamley, M., Wong, M. N., Kylies, D., Gräfe, S. K., Edenhofer, I., et al. (2024) · Science · doi:10.1126/science.abo7027 · Cited by 96 · see citing works
Decoding immunogenic cell death from a dendritic cell perspective
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Intestinal resident macrophages: Multitaskers of the gut
Viola, M. F., & Boeckxstaens, G. E. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.13843 · Cited by 87 · see citing works
Dendritic cells in systemic lupus erythematosus: From pathogenesis to therapeutic applications
Liu, J., Zhang, X., & Cao, X. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102856 · Cited by 90 · see citing works
The Mononuclear Phagocytic System. Generation of Diversity
Gordon, S., & Plüddemann, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01893 · Cited by 86 · see citing works
Intestinal Macrophages in Resolving Inflammation
Hine, A. M., & Loke, P. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900345 · Cited by 85 · see citing works
The many ways tissue phagocytes respond to dying cells
Blander, J. M. (2017) · Immunological Reviews · doi:10.1111/imr.12537 · Cited by 84 · see citing works
Snodgrass, R. G., Benatzy, Y., Schmid, T., Namgaladze, D., Mainka, M., Schebb, N. H., Lütjohann, D., & Brüne, B. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00652-4 · Cited by 83 · see citing works
Ho, G., Cartwright, J. A., Thompson, E. J., Bain, C. C., & Rossi, A. G. (2020) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaa045 · Cited by 81 · see citing works
Chimeric efferocytic receptors improve apoptotic cell clearance and alleviate inflammation
Morioka, S., Kajioka, D., Yamaoka, Y., Ellison, R. M., Tufan, T., Werkman, I. L., Tanaka, S., Barron, B. J., Ito, S., Kucenas, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.11.029 · Cited by 84 · see citing works
Inhaled Pro‐Efferocytic Nanozymes Promote Resolution of Acute Lung Injury
Ji, H., Zhang, C., Xu, F., Mao, Q., Ran, X., Chen, M., Wang, W., Lv, S., Li, W., & Shi, X. (2022) · Advanced Science · doi:10.1002/advs.202201696 · Cited by 83 · see citing works
Striking a balance: new perspectives on homeostatic dendritic cell maturation
Bosteels, V., & Janssens, S. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01079-5 · Cited by 81 · see citing works
Host–Parasite Interactions Promote Disease Tolerance to Intestinal Helminth Infection
King, I. L., & Li, Y.-H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02128 · Cited by 58 · see citing works
At the Forefront of the Mucosal Barrier: The Role of Macrophages in the Intestine
Ruder, B., & Becker, C. (2020) · Cells · doi:10.3390/cells9102162 · Cited by 77 · see citing works
Targeting senescent cells to attenuate cardiovascular disease progression
Song, P., Zhao, Q., & Zou, M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101072 · Cited by 76 · see citing works
On cell death in the intestinal epithelium and its impact on gut homeostasis
Blander, J. M. (2018) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000481 · Cited by 71 · see citing works
Ariyaratne, A., & Finney, C. A. M. (2019) · Infection and Immunity · doi:10.1128/iai.00127-19 · Cited by 67 · see citing works
Determining the effector response to cell death
Rothlin, C. V., Hille, T. D., & Ghosh, S. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00456-0 · Cited by 68 · see citing works
Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease
Lu, H.-Y., Suo, Z., Lin, J., Cong, Y.-Z., & Liu, Z.-J. (2024) · Biomarker Research · doi:10.1186/s40364-024-00612-x · Cited by 67 · see citing works
Functional Circuitry of Neuro-Immune Communication in the Mesenteric Lymph Node and Spleen
Murray, K. M., Barboza, M., Rude, K. M., Brust‐Mascher, I., & Reardon, C. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.188 · Cited by 64 · see citing works
A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival
Kattah, M. G., Shao, L., Rosli, Y. Y., Shimizu, H., Whang, M. I., Advincula, R., Achacoso, P., Shah, S. B., Duong, B. H., Onizawa, M., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180198 · Cited by 59 · see citing works
Macrophage COX2 Mediates Efferocytosis, Resolution Reprogramming, and Intestinal Epithelial Repair
Meriwether, D., Jones, A. E., Ashby, J. W., Solórzano-Vargas, R. S., Dorreh, N., Noori, S., Grijalva, V. R., Ball, A. B., Semis, M., Divakaruni, A. S., et al. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.01.002 · Cited by 59 · see citing works
Wu, S.-M., Fang, X.-Y., Zhao, J.-F., Liu, G., & Liao, P. (2025) · Toxicon · doi:10.1016/j.toxicon.2025.108434 · Cited by 58 · see citing works
Rethinking Phagocytes: Clues from the Retina and Testes
Penberthy, K. K., Lysiak, J. J., & Ravichandran, K. S. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.01.004 · Cited by 57 · see citing works
Iron Handling in Tumor-Associated Macrophages—Is There a New Role for Lipocalin-2?
Jung, M., Weigert, A., Mertens, C., Rehwald, C., & Brüne, B. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01171 · Cited by 54 · see citing works
Stromal regulation of the intestinal barrier
Sylvestre, M., Carlo, S. E. D., & Peduto, L. (2023) · Mucosal Immunology · doi:10.1016/j.mucimm.2023.01.006 · Cited by 50 · see citing works
The renaissance of oral tolerance: merging tradition and new insights
Cerovic, V., Pabst, O., & Mowat, A. M. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01077-7 · Cited by 50 · see citing works
Voisin, B., Nadella, V., Doebel, T., Goel, S., Sakamoto, K., Ayush, O., Jo, J., Kelly, M. C., Kobayashi, T., Jiang, J. X., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.06.006 · Cited by 48 · see citing works
Yang, Z., Li, Q., Wang, X., Jiang, X., Zhao, D., Lin, X., He, F., & Tang, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804094115 · Cited by 46 · see citing works
Macrophage Efferocytosis in Cardiac Pathophysiology and Repair
Li, Y., Li, Q., & Fan, G. (2020) · Shock · doi:10.1097/shk.0000000000001625 · Cited by 46 · see citing works
Nakawesi, J., This, S., Hütter, J., Boucard-Jourdin, M., Barateau, V., Muleta, K. G., Gooday, L. J., Thomsen, K., López, A. G., Ulmert, I., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0276-8 · Cited by 44 · see citing works
The intestinal microenvironment shapes macrophage and dendritic cell identity and function
Filardy, A. A., Ferreira, J. R. M., Rezende, R. M., Kelsall, B. L., & de Oliveira, R. P. (2023) · Immunology Letters · doi:10.1016/j.imlet.2023.01.003 · Cited by 48 · see citing works
Wang, E.-J., Wu, M.-Y., Ren, Z., Zheng, Y., Ye, R. D., Tan, C. S. H., Wang, Y., & Lu, J. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad004 · Cited by 43 · see citing works
Beyond Immunity: Underappreciated Functions of Intestinal Macrophages
Chiaranunt, P., Tai, S. L., Ngai, L., & Mortha, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.749708 · Cited by 38 · see citing works
Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition
Stephens, W. Z., Kubinak, J. L., Ghazaryan, A., Bauer, K. M., Bell, R. S., Buhrke, K., Chiaro, T. R., Weis, A. M., Tang, W. W., Monts, J. K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109916 · Cited by 38 · see citing works
Intestinal Macrophages at the Crossroad between Diet, Inflammation, and Cancer
Caprara, G., Allavena, P., & Erreni, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144825 · Cited by 38 · see citing works
Epithelial Pyroptosis in Host Defense
Churchill, M. J., Mitchell, P. S., & Rauch, I. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167278 · Cited by 38 · see citing works
Microbiota-mediated mechanisms of mucosal immunity across the lifespan
Iliev, I. D., Blander, J. M., Collins, N., Guo, C., Longman, R., Sonnenberg, G. F., Zeng, M. Y., & Artis, D. (2025) · Nature Immunology · doi:10.1038/s41590-025-02281-w · Cited by 43 · see citing works
Tyro3, Axl, Mertk receptor-mediated efferocytosis and immune regulation in the tumor environment
Zhou, L., & Matsushima, G. K. (2021) · International review of cytology · doi:10.1016/bs.ircmb.2021.02.002 · Cited by 35 · see citing works
The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis
Zhang, X., Yu, Z., Chen, J., Li, X., Wang, Z.-P., Wu, M., & Liu, L. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106289 · Cited by 33 · see citing works
Strohmeier, V., Andrieux, G., Unger, S., Reguant, A. P., Klocperk, A., Seidl, M., Cabral-Marques, O., Eckert, M., Gräwe, K., Shabani, M., et al. (2022) · Journal of Clinical Immunology · doi:10.1007/s10875-022-01379-2 · Cited by 34 · see citing works
From birth to death: The hardworking life of Paneth cell in the small intestine
Cui, C., Wang, F., Zheng, Y., Wei, H., & Peng, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1122258 · Cited by 34 · see citing works
Controlling Hair Loss by Regulating Apoptosis in Hair Follicles: A Comprehensive Overview
Wang, W., Wang, H.-L., Long, Y., Li, Z., & Li, J. (2023) · Biomolecules · doi:10.3390/biom14010020 · Cited by 34 · see citing works
Toward the Characterization of Human Pro-Resolving Macrophages?
Saas, P., Chagué, C., Maraux, M., & Cherrier, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.593300 · Cited by 32 · see citing works
TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn’s Disease Patients
Caër, C., Gorreja, F., Forsskåhl, S. K., Brynjolfsson, S. F., Szeponik, L., Magnusson, M. K., Börjesson, L. G., Block, M., Lindskog, E. B., & Wick, M. J. (2021) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjab022 · Cited by 32 · see citing works
- Authors
- Cummings, R. J., Barbet, G., Bongers, G., Hartmann, B. M., Gettler, K., Muniz, L., Furtado, G. C., Cho, J., Lira, S. A., & Blander, J. M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Yale University (US)
- Tisch Cancer Institute (US)
- Corresponding author
- Blander, J. Magarian
- Venue
- Nature
- Published
- 2016-11
- Volume
- 539
- Issue
- 7630
- Pages
- 565-569
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5807003
- OpenAlex
- W2556519132
- Cited by
- 228
- References
- 35
- Citations by year
- 2026: 23 · 2025: 20 · 2024: 22 · 2023: 21 · 2022: 26 · 2021: 25 · 2020: 32 · 2019: 21 · 2018: 17 · 2017: 21
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Crohn's and Colitis Foundation (294024)
- National Institutes of Health (5r01dk092235-06, 2T32A1007605-11, DK072201)
- National Cancer Institute (R01CA161373)
- National Institute of Allergy and Infectious Diseases (HHSN272201000054C, U19AI117873, R01AI095245, R01AI123284)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK092235, R01DK111862, T32DK007792, P01DK072201, U01DK062429, U01DK062422, R01DK110352)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007149)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- efferocytosis, intestinal epithelial cells, dendritic cells, macrophage subsets, regulatory T cells, self-tolerance, mesenteric lymph nodes, tissue homeostasis, lipid metabolism, amino acid catabolism, chronic intestinal inflammation, autoimmunity
- MeSH terms
- Amino Acids, Animals, Cell Differentiation, Cell Movement, Dendritic Cells, Epithelial Cells, Female, Homeostasis, Inflammation, Intestinal Mucosa, Lymph Nodes, Lymphocyte Activation, Macrophages, Male, Phagocytes, Transcription, Genetic, Inflammatory Bowel Diseases, CD4-Positive T-Lymphocytes, Antigens, CD, Apoptosis, Integrin alpha Chains, Lipid Metabolism, T-Lymphocytes, Regulatory, Mice
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