Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes
Open accessAbstract
The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Their constant presence within the liver is not mere confinement; it is a strategic placement, ensuring they are the frontline defence against pathogens and tissue damage.
“Their constant presence within the liver is not mere confinement; it is a strategic placement, ensuring they are the frontline defence against pathogens and tissue damage(108-110).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [109]
The Introduction calls liver-resident immune cells “frontline human liver sentinels” and describes tissue-resident T cells as important for pathogen surveillance. The Results and discussion also link their longevity to sustained surveillance of residual virus or tumor. The paper does not establish that their placement is a defense against tissue damage; it instead discusses preserving organ integrity while recognizing that immune responses can be pathogenic. Page numbers are unavailable in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245 · see citing works
Self-citationA Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · see citing works
Davies, L. C., Jenkins, S. J., Allen, J. E., & Taylor, P. R. (2013) · Nature Immunology · doi:10.1038/ni.2705 · Cited by 2,096 · see citing works
Tissue-Resident Macrophage Ontogeny and Homeostasis
Ginhoux, F., & Guilliams, M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.024 · Cited by 1,884 · see citing works
Resolving the fibrotic niche of human liver cirrhosis at single-cell level
Ramachandran, P., Dobie, R., Wilson-Kanamori, J. R., Dora, E. F., Henderson, B. E. P., Luu, N. T., Portman, J. R., Matchett, K. P., Brice, M., Marwick, J. A., et al. (2019) · Nature · doi:10.1038/s41586-019-1631-3 · Cited by 1,784 · see citing works
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
MacParland, S. A., Liu, J. C., Ma, X.-Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06318-7 · Cited by 1,552 · see citing works
Liver Macrophages in Tissue Homeostasis and Disease
Krenkel, O., & Tacke, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.11 · Cited by 1,424 · see citing works
A human liver cell atlas reveals heterogeneity and epithelial progenitors
Aizarani, N., Saviano, A., Sagar, Mailly, L., Durand, S., Herman, J. S., Pessaux, P., Baumert, T. F., & Grün, D. (2019) · Nature · doi:10.1038/s41586-019-1373-2 · Cited by 1,147 · see citing works
Kumar, B. V., Ma, W., Miron, M., Granot, T., Guyer, R. S., Carpenter, D. J., Senda, T., Sun, X., Ho, S.-H., Lerner, H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.078 · Cited by 1,068 · see citing works
Developmental and Functional Heterogeneity of Monocytes
Guilliams, M., Mildner, A., & Yona, S. (2018) · Immunity · doi:10.1016/j.immuni.2018.10.005 · Cited by 973 · see citing works
Self-citationSpecification of tissue-resident macrophages during organogenesis
Mass, E., Ballesteros, I., Farlik, M., Halbritter, F., Günther, P., Crozet, L., Jacome-Galarza, C. E., Händler, K., Klughammer, J., Kobayashi, Y., et al. (2016) · Science · doi:10.1126/science.aaf4238 · Cited by 891 · see citing works
Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells
Scott, C. L., Zheng, F., De Baetselier, P., Martens, L., Saeys, Y., De Prijck, S., Lippens, S., Abels, C., Schoonooghe, S., Raes, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms10321 · Cited by 860 · see citing works
Limmer, A., Ohl, J., Kurts, C., Ljunggren, H.-G., Reiss, Y., Groettrup, M., Momburg, F., Arnold, B., & Knolle, P. A. (2000) · Nature Medicine · doi:10.1038/82161 · Cited by 758 · cited 1× · see citing works
“…and the specialized liver sinusoidal endothelium equip this organ with a unique capacity to prime T cells; KCs are able to prime effective CD8+ T cells, whereas priming by liver sinusoidal endothelium or hepatocytes leads to dysfunctional responses (Bénéchet et al., 2019; Limmer et al., 2000).”
BackgroundThe human heart contains distinct macrophage subsets with divergent origins and functions
Bajpai, G., Schneider, C., Wong, N., Bredemeyer, A., Hulsmans, M., Nahrendorf, M., Epelman, S., Kreisel, D., Liu, Y., Itoh, A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0059-x · Cited by 712 · see citing works
Location, location, location: Tissue resident memory T cells in mice and humans
Szabo, P. A., Miron, M., & Farber, D. L. (2019) · Science Immunology · doi:10.1126/sciimmunol.aas9673 · Cited by 651 · see citing works
Tissue-Resident T Cells and Other Resident Leukocytes
Masopust, D., & Soerens, A. G. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053214 · Cited by 608 · see citing works
Decoding human fetal liver haematopoiesis
Popescu, D.-M., Botting, R. A., Stephenson, E., Green, K., Webb, S., Jardine, L., Calderbank, E. F., Polanski, K., Goh, I., Efremova, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1652-y · Cited by 606 · see citing works
Living in the liver: hepatic infections
Protzer, U., Maini, M. K., & Knolle, P. A. (2012) · Nature reviews. Immunology · doi:10.1038/nri3169 · Cited by 561 · see citing works
Self-citationKrenkel, O., Puengel, T., Govaere, O., Abdallah, A. T., Mossanen, J. C., Kohlhepp, M., Liepelt, A., Lefebvre, E., Luedde, T., Hellerbrand, C., et al. (2018) · Hepatology · doi:10.1002/hep.29544 · Cited by 557 · see citing works
Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection
Fernandez-Ruiz, D., Ng, W. Y., Holz, L. E., Ma, J. Z., Zaid, A., Wong, Y. C., Lau, L. S., Mollard, V., Cozijnsen, A., Collins, N., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.08.011 · Cited by 438 · cited 2× · see citing works
“Although hepatic CD8+ T cells can reside within the sinusoidal vasculature (Fernandez-Ruiz et al., 2016), if some transmigrate through the hepatic endothelium, they would be expected to exit the liver via the lymphatic drainage into local lymph nodes, rather than directly into the hepatic vein.”
BackgroundSakai, M., Troutman, T. D., Seidman, J. S., Ouyang, Z., Spann, N. J., Abe, Y., Ego, K. M., Bruni, C. M., Deng, Z., Schlachetzki, J. C. M., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.002 · Cited by 418 · see citing works
Resident human hepatitis lymphocytes are phenotypically different from circulating lymphocytes
Norris, S., Collins, C., Doherty, D. G., Smith, F., McEntee, G., Traynor, O., Nolan, N., Hegarty, J., & O'Farrelly, C. (1998) · Journal of Hepatology · doi:10.1016/s0168-8278(98)80206-7 · Cited by 374 · see citing works
Hallmarks of Tissue-Resident Lymphocytes
Fan, X., & Rudensky, A. Y. (2016) · Cell · doi:10.1016/j.cell.2016.02.048 · Cited by 352 · see citing works
IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection
Pallett, L. J., Davies, J., Colbeck, E. J., Robertson, F., Hansi, N., Easom, N. J. W., Burton, A. R., Stegmann, K. A., Schurich, A., Swadling, L., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162115 · Cited by 347 · see citing works
Self-citationKlein, I., Cornejo, J. C., Polakos, N. K., John, B., Wuensch, S. A., Topham, D. J., Pierce, R. H., & Crispe, I. N. (2007) · Blood · doi:10.1182/blood-2007-02-073841 · Cited by 326 · see citing works
Allo-HLA reactivity of virus-specific memory T cells is common.
Amir, A., D'Orsogna, L. J., Roelen, D., van Loenen, M. V., Hagedoorn, R., de Boer, R., van der Hoorn, M., Kester, M., Doxiadis, I. I. N., Falkenburg, J. F. F., et al. (2010) · Blood · doi:10.1182/blood-2009-07-234906 · Cited by 315 · see citing works
Generation and persistence of human tissue-resident memory T cells in lung transplantation
Snyder, M. E., Finlayson, M. O., Connors, T. J., Dogra, P., Senda, T., Bush, E. C., Carpenter, D. J., Marboe, C. C., Benvenuto, L. J., Shah, L., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav5581 · Cited by 281 · see citing works
T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells
Beura, L. K., Wijeyesinghe, S., Thompson, E. A., Macchietto, M. G., Rosato, P. C., Pierson, M. J., Schenkel, J. M., Mitchell, J. S., Vezys, V., Fife, B. T., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.015 · Cited by 262 · see citing works
Sierro, F., Evrard, M., Rizzetto, S., Melino, M., Mitchell, A. J., Flórido, M., Beattie, L., Walters, S. B., Tay, S. S., Lü, B., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.018 · Cited by 256 · see citing works
Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
Bénéchet, A. P., De Simone, G., Di Lucia, P., Cilenti, F., Barbiera, G., Le Bert, N., Fumagalli, V., Lusito, E., Moalli, F., Bianchessi, V., et al. (2019) · Nature · doi:10.1038/s41586-019-1620-6 · Cited by 222 · cited 1× · see citing works
“…and the specialized liver sinusoidal endothelium equip this organ with a unique capacity to prime T cells; KCs are able to prime effective CD8+ T cells, whereas priming by liver sinusoidal endothelium or hepatocytes leads to dysfunctional responses (Bénéchet et al., 2019; Limmer et al., 2000).”
BackgroundMucosal Resident Memory CD4 T Cells in Protection and Immunopathology
Turner, D., & Färber, D. L. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00331 · Cited by 198 · see citing works
Buggert, M., Nguyen, S., de Oca, G. S. M., Bengsch, B., Darko, S. W., Ransier, A., Roberts, E. R., Alcazar, D. D., Brody, I. B., Vella, L. A., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aar4526 · Cited by 162 · see citing works
Tse, S., Radtke, A. J., Espinosa, D. A., Cockburn, I. A., & Zavala, F. P. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiu281 · Cited by 158 · see citing works
Resident memory CD8 T cells persist for years in human small intestine
Bartolomé-Casado, R., Landsverk, O. J. B., Chauhan, S. K., Richter, L., Phung, D., Greiff, V., Risnes, L. F., Yao, Y., Neumann, R. S., Yaqub, S., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190414 · Cited by 152 · see citing works
Cuff, A. O., Robertson, F. P., Stegmann, K. A., Pallett, L. J., Maini, M. K., Davidson, B. R., & Male, V. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1601424 · Cited by 116 · see citing works
Self-citationThe role of Kupffer cells in hepatic iron and lipid metabolism
Scott, C. L., & Guilliams, M. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.02.013 · Cited by 97 · see citing works
High Frequency of Chimerism in Transplanted Livers
Ng, I. O., Chan, K.-L., Shek, W.-H., Lee, J. M.-F., Fong, D. Y.-T., Lo, C.-M., & Fan, S.-T. (2003) · Hepatology · doi:10.1053/jhep.2003.50395 · Cited by 94 · see citing works
Miron, M., Kumar, B. V., Meng, W., Granot, T., Carpenter, D. J., Senda, T., Chen, D., Rosenfeld, A. M., Zhang, B., Lerner, H., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800716 · Cited by 78 · see citing works
Kim, J. H., Han, J. W., Choi, Y. J., Rha, M.-S., Koh, J. Y., Kim, K. H., Kim, C. G., Lee, Y. J., Kim, A. R., Park, J., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.01.010 · Cited by 61 · see citing works
Rosen, H. R., Hinrichs, D. J., Leistikow, R. L., Callender, G. G., Wertheimer, A. M., Nishimura, M. I., & Lewinsohn, D. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.9.5355 · Cited by 48 · see citing works
Implications of Resident Memory T Cells for Transplantation
Beura, L. K., Rosato, P. C., & Masopust, D. (2016) · American Journal of Transplantation · doi:10.1111/ajt.14101 · Cited by 39 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Immunotherapies for hepatocellular carcinoma
Llovet, J. M., Castet, F., Heikenwalder, M., Maini, M. K., Mazzaferro, V., Pinato, D. J., Pikarsky, E., Zhu, A. X., & Finn, R. S. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00573-2 · Cited by 1,843 · see citing works
Self-citationSpatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., Bujko, A., Martens, L., Thoné, T., Browaeys, R., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.018 · Cited by 985 · see citing works
Peiseler, M., Schwabe, R., Hampe, J., Kubes, P., Heikenwälder, M., & Tacke, F. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.012 · Cited by 564 · see citing works
Liver macrophages in health and disease
Guilliams, M., & Scott, C. L. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.002 · Cited by 395 · see citing works
Künzli, M., & Masopust, D. (2023) · Nature Immunology · doi:10.1038/s41590-023-01510-4 · Cited by 338 · see citing works
Macrophage functional diversity in NAFLD — more than inflammation
Barreby, E., Chen, P., & Aouadi, M. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00675-6 · Cited by 246 · see citing works
Tissue-resident memory T cells in tumor immunity and immunotherapy
Okła, K., Färber, D. L., & Zou, W. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201605 · Cited by 230 · see citing works
A guide to adaptive immune memory
Lam, N., Lee, Y. S., & Färber, D. L. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01040-6 · Cited by 217 · see citing works
Patel, A. A., Ginhoux, F., & Yona, S. (2021) · Immunology · doi:10.1111/imm.13320 · Cited by 203 · see citing works
Self-citationZhang, C., Li, J., Cheng, Y., Meng, F., Song, J., Fan, X., Fan, H., Li, J., Fu, Y., Zhou, M., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-325915 · Cited by 198 · see citing works
Tissue-resident immune cells in humans
Gray, J. I., & Farber, D. L. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-112809 · Cited by 181 · see citing works
The scientific basis of combination therapy for chronic hepatitis B functional cure
Lim, S. G., Baumert, T. F., Boni, C., Gane, E. J., Levrero, M., Lok, A. S.-F., Maini, M. K., Terrault, N. A., & Zoulim, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00724-5 · Cited by 176 · see citing works
Self-citationResident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma
Molodtsov, A. K., Khatwani, N., Vella, J. L., Lewis, K. A., Zhao, Y., Han, J., Sullivan, D. E., Searles, T. G., Preiss, N. K., Shabaneh, T. B., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.08.019 · Cited by 155 · see citing works
Localization, tissue biology and T cell state — implications for cancer immunotherapy
Schenkel, J. M., & Pauken, K. E. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00884-8 · Cited by 139 · see citing works
Zakeri, N., Hall, A. R., Swadling, L., Pallett, L. J., Schmidt, N. M., Diniz, M. O., Kucykowicz, S., Amin, O. E., Gander, A., Pinzani, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29012-1 · Cited by 135 · see citing works
Self-citationBurton, O. T., Bricard, O., Tareen, S. H. K., Gergelits, V., Andrews, S. R., Biggins, L., Roca, C. P., Whyte, C., Junius, S., Brajic, A., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.05.023 · Cited by 84 · see citing works
Cheng, M. L., Nakib, D., Perciani, C. T., & MacParland, S. A. (2021) · Clinical Science · doi:10.1042/cs20190654 · Cited by 122 · see citing works
Human circulating and tissue-resident memory CD8+ T cells
Buggert, M., Price, D. A., Mackay, L. K., & Betts, M. R. (2023) · Nature Immunology · doi:10.1038/s41590-023-01538-6 · Cited by 119 · see citing works
The expanding world of tissue‐resident macrophages
Jenkins, S. J., & Allen, J. E. (2021) · European Journal of Immunology · doi:10.1002/eji.202048881 · Cited by 105 · see citing works
Macrophages in Organ Transplantation
Ordikhani, F., Pothula, V., Sánchez-Tarjuelo, R., Jordan, S., & Ochando, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.582939 · Cited by 89 · see citing works
Resident memory T cells and cancer
Gavil, N. V., Cheng, K., & Masopust, D. (2024) · Immunity · doi:10.1016/j.immuni.2024.06.017 · Cited by 94 · see citing works
Tissue CD14+CD8+T-cells reprogrammed by myeloid cells and modulated by LPS
Pallett, L., Swadling, L., Diniz, M., Maini, A. A., Schwabenland, M., Gasull, A. D., Davies, J., Kucykowicz, S., Skelton, J., Thomas, N., et al. (2023) · Nature · doi:10.1038/s41586-022-05645-6 · Cited by 68 · see citing works
Self-citationMonocyte differentiation within tissues: a renewed outlook
Rigamonti, A., Villar, J., & Segura, É. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.10.005 · Cited by 63 · see citing works
NUDT1 promotes the accumulation and longevity of CD103+ TRM cells in primary biliary cholangitis
Huang, B., Lyu, Z., Qian, Q., Chen, Y., Zhang, J., Li, B., Li, Y., Liang, J., Liu, Q., Li, Y., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.014 · Cited by 60 · see citing works
The human liver microenvironment shapes the homing and function of CD4 + T-cell populations
Wiggins, B. G., Pallett, L. J., Li, X., Davies, S. P., Amin, O. E., Gill, U. S., Kucykowicz, S., Patel, A. M., Aliazis, K., Liu, Y. S., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-323771 · Cited by 55 · see citing works
Self-citationAirway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2
Diniz, M. O., Mitsi, E., Swadling, L., Rylance, J., Johnson, M., Goldblatt, D., Ferreira, D. M., & Maini, M. K. (2022) · Nature Immunology · doi:10.1038/s41590-022-01292-1 · Cited by 55 · see citing works
Self-citationKefalakes, H., Horgan, X. J., Jung, M. K., Amanakis, G., Kapuria, D., Bolte, F. J., Kleiner, D. E., Koh, C., Heller, T., & Rehermann, B. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.027 · Cited by 56 · see citing works
de Almeida, G. P., Lichtner, P., Eckstein, G., Brinkschmidt, T., Chu, C.-F., Sun, S., Reinhard, J., Mädler, S. C., Kloeppel, M., Verbeek, M., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abe2634 · Cited by 55 · see citing works
Priming and Maintenance of Adaptive Immunity in the Liver
Kawashima, K., Andreata, F., Beccaría, C. G., & Iannacone, M. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090122-041354 · Cited by 55 · see citing works
Macrophages as key regulators of liver health and disease
Papachristoforou, E., & Ramachandran, P. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.006 · Cited by 55 · see citing works
Immunotherapy and Liver Transplantation: A Narrative Review of Basic and Clinical Data
Wassmer, C., Hajji, S. E., Papazarkadas, X., Compagnon, P., Tabrizian, P., Lacotte, S., & Toso, C. (2023) · Cancers · doi:10.3390/cancers15184574 · Cited by 52 · see citing works
The liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59 · see citing works
An Eye on Kupffer Cells: Development, Phenotype and the Macrophage Niche
Elchaninov, A. V., Vishnyakova, P., Menyailo, E., Sukhikh, G. T., & Fatkhudinov, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179868 · Cited by 47 · see citing works
Human T lymphocytes at tumor sites
Notarbartolo, S., & Abrignani, S. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00970-4 · Cited by 47 · see citing works
Insights into phenotypic and functional CD8 + TRM heterogeneity
Heeg, M., & Goldrath, A. W. (2023) · Immunological Reviews · doi:10.1111/imr.13218 · Cited by 44 · see citing works
van Gisbergen, K. P. J. M., Zens, K. D., & Münz, C. (2021) · European Journal of Immunology · doi:10.1002/eji.202049062 · Cited by 39 · see citing works
Heterogeneity of tissue resident memory T cells
Konjar, Š., Ficht, X., Iannacone, M., & Veldhoen, M. (2022) · Immunology Letters · doi:10.1016/j.imlet.2022.02.009 · Cited by 39 · see citing works
Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists
Bartsch, L., Damasio, M., Subudhi, S., & Drescher, H. K. (2020) · Cells · doi:10.3390/cells9112457 · Cited by 41 · see citing works
Emerging Concepts of Tissue-resident Memory T Cells in Transplantation
Fu, J., & Sykes, M. (2021) · Transplantation · doi:10.1097/tp.0000000000004000 · Cited by 39 · see citing works
Li, X., Li, S., Wang, Y., Zhou, X., Wang, F., Muhammad, I., Luo, Y., Yandong, S., Liu, D., Wu, B., et al. (2024) · Theranostics · doi:10.7150/thno.96928 · Cited by 36 · see citing works
Petrash, C. C., Palestine, A. G., & Canto-Soler, M. V. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.621007 · Cited by 35 · see citing works
Two sides of the same coin: Protective versus pathogenic CD4 + resident memory T cells
Oja, A. E., van Lier, R. A. W., & Hombrink, P. (2022) · Science Immunology · doi:10.1126/sciimmunol.abf9393 · Cited by 34 · see citing works
Resilience of dermis resident macrophages to inflammatory challenges
Lee, S. H., & Sacks, D. L. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01313-z · Cited by 33 · see citing works
Immunologic role of macrophages in sepsis-induced acute liver injury
Xu, W., Hou, H., Yang, W., Tang, W., & Sun, L. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113492 · Cited by 29 · see citing works
Tian, Q., Zhang, Z., Tan, L., Yang, F., Xu, Y., Guo, Y., Wei, D., Wu, C., Cao, P., Ji, J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abk0270 · Cited by 29 · see citing works
Tissue-resident memory T cells in chronic liver diseases: Phenotype, development and function
Li, Y.-K., You, Z., Tang, R., & Ma, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.967055 · Cited by 24 · see citing works
Liver-resident memory T cells: life in lockdown
Pallett, L. J., & Maini, M. K. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00932-w · Cited by 28 · see citing works
Self-citationAntigen reactivity defines tissue-resident memory and exhausted T cells in tumors
Burn, T. N., Schröder, J., Gandolfo, L. C., Osman, M., Wainwright, E. N., Lam, E. Y. N., McDonald, K. M., Evans, R., Li, S., Rawlinson, D., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02347-9 · Cited by 32 · see citing works
Wang, Y., Zhang, H., Du, G., Luo, H., Su, J., Sun, Y., Zhou, M., Shi, B., Li, H. Q. X., Jiang, H., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.12.009 · Cited by 28 · see citing works
Tissue-resident and innate-like T cells in patients with advanced chronic liver disease
Ibidapo-Obe, O., & Bruns, T. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100812 · Cited by 25 · see citing works
Axes of heterogeneity in human tissue‐resident memory T cells
Szabo, P. A. (2023) · Immunological Reviews · doi:10.1111/imr.13210 · Cited by 25 · see citing works
Memories that last: Dynamics of memory T cells throughout the body
Derksen, L. Y., Tesselaar, K., & Borghans, J. A. M. (2023) · Immunological Reviews · doi:10.1111/imr.13211 · Cited by 23 · see citing works
Li, Y., Li, B., Xiao, X., Qian, Q., Wang, R., Lyu, Z., Chen, R., Cui, N., Ou, Y., Pu, X., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000549 · Cited by 24 · see citing works
Immunobiology of the biliary tract system
Björkström, N. K. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.08.018 · Cited by 24 · see citing works
Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers
David, B. A., Andreata, F., Blériot, C., Ginhoux, F., Kubes, P., & Iannacone, M. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01288-0 · Cited by 22 · see citing works
Mucosal Immunity against SARS-CoV-2 in the Respiratory Tract
Noh, H. E., & Rha, M. (2024) · Pathogens · doi:10.3390/pathogens13020113 · Cited by 20 · see citing works
Noé, A., Datoo, M., Flaxman, A., Husainy, M. A., Jenkin, D., Bellamy, D., Makinson, R., Morter, R., Ramos-Lopez, F., Sheridan, J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.795463 · Cited by 18 · see citing works
Mittra, S., Harding, S. M., & Kaech, S. M. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2300049 · Cited by 19 · see citing works
Argemí, J., Ponz‐Sarvisé, M., & Sangro, B. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2022.03.002 · Cited by 19 · see citing works
Pop, O.-T., Geng, A., Flint, E., Singanayagam, A., Ercan, C., Possamai, L. A., Patel, V., Künzler‐Heule, P., Meier, M., Soysal, S. D., et al. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.03.007 · Cited by 18 · see citing works
Cardon, A., Guinebretière, T., Dong, C., Gil, L., Ado, S., Gavlovsky, P.-J., Braud, M., Danger, R., Schultheiß, C., Doméné, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56363-2 · Cited by 22 · see citing works
Personalized Immunity: Neoantigen-Based Vaccines Revolutionizing Hepatocellular Carcinoma Treatment
Aggeletopoulou, I., Pantzios, S., & Triantos, C. K. (2025) · Cancers · doi:10.3390/cancers17030376 · Cited by 17 · see citing works
Ahamed, F., Eppler, N., Jones, E., & Zhang, Y. (2024) · Livers · doi:10.3390/livers4030033 · Cited by 14 · see citing works
Human resident liver myeloid cells protect against metabolic stress in obesity
Barreby, E., Strunz, B., Nock, S., Naudet, L., Shen, J. X., Johansson, H., Sönnerborg, I., Ma, J., Urgard, E., Pallett, L. J., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00834-7 · Cited by 15 · see citing works
Self-citationPeters, A. L., DePasquale, E. A. K., Begum, G., Roskin, K. M., Kotliar, M., Barski, A., Salomonis, N., Shi, T., Ranganathan, S., Woodle, E. S., et al. (2025) · American Journal of Transplantation · doi:10.1016/j.ajt.2025.08.004 · Cited by 14 · see citing works
Zarlashat, Y., Ghaffar, A., Guerra, F., & Picca, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167836 · Cited by 18 · see citing works
GM-CSF distinctly impacts human monocytes and macrophages via ERK1/2-dependent pathways
Farzam‐kia, N., Moratalla, A. C., Lemaître, F., Levert, A., Cal, S. D., Margarido, C., Solorio, Y. C., & Arbour, N. (2023) · Immunology Letters · doi:10.1016/j.imlet.2023.07.009 · Cited by 14 · see citing works
Wu, L., Deng, H., Feng, X., Xie, D., Li, Z., Chen, J., Mo, Z., Zhao, Q., Hu, Z., Yi, S., et al. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29627 · Cited by 14 · see citing works
Tissue-resident memory CD8+ T cells: master deciphers of the hepatic environment
Romero, D. B., Finney, G. E., Dudek, M., & Pallett, L. (2025) · Nature reviews: Gastroenterology & hepatology · doi:10.1038/s41575-025-01118-z · Cited by 11 · see citing works
Self-citationTransient tissue residency and lymphatic egress define human CD56bright NK cell homeostasis
Niehrs, A., Hertwig, L., Buggert, M., Nordström, I., Statzu, M., Pampena, M. B., Samer, S., Knox, J. J., Strunz, B., Sun, D., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02290-9 · Cited by 13 · see citing works
Liver Macrophage Diversity in Health and Disease
Horn, P., & Tacke, F. (2024) · Results and problems in cell differentiation · doi:10.1007/978-3-031-65944-7_7 · Cited by 14 · see citing works
Prosser, A., Huang, W.-H., Liu, L., Dart, S. J., Watson, M., de Boer, B., Kendrew, P., Lucas, A., Larma-Cornwall, I., Gaudieri, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109141 · Cited by 14 · see citing works
Rahmberg, A. R., Wu, C., Shin, T., Hong, S. G., Pei, L., Markowitz, T. E., Hickman, H. D., Dunbar, C. E., & Brenchley, J. M. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023011499 · Cited by 13 · see citing works
Resident Memory T Cells and Their Role within the Liver
Ghilas, S., Valencia‐Hernandez, A. M., Enders, M. H., Heath, W. R., & Fernandez‐Ruiz, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228565 · Cited by 13 · see citing works
Valencia-Hernandez, A., Zillinger, T., Ge, Z.-Y., Tan, P., Cozijnsen, A., McFadden, G. I., Lahoud, M., Caminschi, I., Barchet, W., Heath, W., et al. (2023) · Vaccine · doi:10.1016/j.vaccine.2022.12.047 · Cited by 10 · see citing works
Stein, J., Ruef, N., & Wissmann, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.626019 · Cited by 10 · see citing works
Colombo, S. A. P., Brown, S. L., Hepworth, M. R., Hankinson, J., Granato, F., Kitchen, S. J., Hussell, T., Simpson, A., Cook, P. C., & MacDonald, A. S. (2023) · Discovery Immunology · doi:10.1093/discim/kyad009 · Cited by 10 · see citing works
T cell trafficking in human chronic inflammatory diseases
Giovenzana, A., Codazzi, V., Pandolfo, M., & Petrelli, A. (2024) · iScience · doi:10.1016/j.isci.2024.110528 · Cited by 11 · see citing works
Li, J., Lv, M., Huang, Q., Hu, R., Zhong, X., Sun, X., Feng, W., Han, Z., Ma, M., Zhang, W., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-42560-w · Cited by 10 · see citing works
Rethinking Immune Check Point Inhibitors Use in Liver Transplantation: Implications and Resistance
Ortiz, V., & Loeuillard, E. J. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101407 · Cited by 10 · see citing works
Li, X., Wu, J., Zhu, S., Wei, Q., Wang, L., & Chen, J. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04846-0 · Cited by 10 · see citing works
Harnessing liver-resident memory T cells for protection against malaria
Fernandez-Ruiz, D., de Menezes, M. N., Holz, L. E., Ghilas, S., Heath, W., & Beattie, L. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1881485 · Cited by 8 · see citing works
Spatial organization of tissue-resident memory T cells.
Burn, T. N., & Mackay, L. K. (2026) · Immunity · doi:10.1016/j.immuni.2026.03.009 · Cited by 13 · see citing works
Isolation of Lymphocytes from Human Skin and Murine Tissues: A Rapid and Epitope-Preserving Approach
Polakova, A., Hudemann, C., Wiemers, F., Kadys, A., Gremke, N., Lang, M., Zwiorek, L., Pfützner, W., Hertl, M., Möbs, C., et al. (2022) · JID Innovations · doi:10.1016/j.xjidi.2022.100155 · Cited by 8 · see citing works
Kucykowicz, S., Amin, O. E., Burton, A. R., Swadling, L., Schmidt, N. M., Zakeri, N., Davies, J. E., Aidoo-Micah, G., Stegmann, K. A., Easom, N. J. W., et al. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101356 · Cited by 7 · see citing works
Self-citationDart, S., Prosser, A., Huang, W. H., Liu, L., Lucas, A., Delrivière, L., Gaudieri, S., Jeffrey, G. P., & Lucas, M. (2022) · Transplantation · doi:10.1097/tp.0000000000004481 · Cited by 7 · see citing works
CD8+ Trms against malaria liver-stage: prospects and challenges
Zhu, C.-Y., Jiao, S.-M., & Xu, W.-Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1344941 · Cited by 5 · see citing works
Recognizing Complexity of CD8 T Cells in Transplantation
Nicosia, M., & Valujskikh, A. (2024) · Transplantation · doi:10.1097/tp.0000000000005001 · Cited by 6 · see citing works
Cutaneous Immune Memory: A Double-Edged Sword in Skin Repair and Fibrosis
Ghasemishahrestani, Z., Khumalo, N. P., Ipp, H., & Bayat, A. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.09.006 · Cited by 5 · see citing works
Al-Adra, D., Lan, R., Jennings, H., Weinstein, K. N., Liu, Y.-J., Verhoven, B., Zeng, W., Heise, G., Levitsky, M., Chlebeck, P., et al. (2024) · Transplant Immunology · doi:10.1016/j.trim.2024.102104 · Cited by 5 · see citing works
Tolerance in intestinal transplantation
Sykes, M. (2024) · Human Immunology · doi:10.1016/j.humimm.2024.110793 · Cited by 4 · see citing works
Transplant Immunology in Liver Transplant, Rejection, and Tolerance
Yokoyama, M., Imai, D., Wolfe, S., George, L., Sambommatsu, Y., Khan, A. A., Lee, S. D., Saeed, M. I., Sharma, A. K., Kumaran, V., et al. (2024) · Livers · doi:10.3390/livers4030031 · Cited by 4 · see citing works
Understanding Liver Transplantation Outcomes Through the Lens of Its Tissue-resident Immunobiome
Prosser, A., Klenerman, P., & Lucas, M. (2025) · Transplantation · doi:10.1097/tp.0000000000005303 · Cited by 4 · see citing works
Han, J. W., & Shin, E. (2025) · Gut and Liver · doi:10.5009/gnl240366 · Cited by 4 · see citing works
Sibbertsen, F., Dress, R., Weidemann, S., Möller, K., Herden, U., Fischer, L., Paul, K., Oh, J., Tolosa, E., Schulz-Jürgensen, S., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1567645 · Cited by 2 · see citing works
Liu, Y., Zhang, B., Meng, Z., Lei, L., Song, Y., Lan, J., Li, B., Ouyang, C., Yuan, S., Liu, P., et al. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e25-05-0265 · Cited by 3 · see citing works
Reconstitution of the uterine immune milieu after uterus or hematopoietic stem cell transplantation
Strunz, B., Ivarsson, M. A., Sun, D., Mayer, C., Ziegenhain, C., Guterstam, Y. C., Solders, M., Mölne, J., Björklund, A. T., Marquardt, N., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adp2583 · Cited by 3 · see citing works
Advances in innate immune memory of macrophages
Khan, S. U., & Khan, M. U. (2022) · Exploration of Immunology · doi:10.37349/ei.2022.00060 · Cited by 3 · see citing works
Targeting macrophages in liver fibrosis
González del Barrio, L., Ipsen, D. H., Pfister, D. R., Hancz, D., & Scott, C. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835489 · Cited by 3 · see citing works
“During homeostasis, monocyte contribution to KCs is limited, even in humans (102), and is rather restricted to the minor populations of capsule, central vein, and bile-duct macrophages (for more information on these minor populations, we refer to the review of liver macrophages in health and…”
Diamond, T., Chapin, C. A., Diorio, C. J., McCuaig, S., Lau, M., Chu, N., Gibson, N. M., Kreiger, P. A., Horslen, S. P., Loomes, K. M., et al. (2026) · Hepatology Communications · doi:10.1097/hc9.0000000000000926 · Cited by 2 · see citing works
- Authors
- Pallett, L. J., Burton, A. R., Amin, O. E., Rodriguez-Tajes, S., Patel, A. A., Zakeri, N., Jeffery-Smith, A., Swadling, L., Schmidt, N. M., Baiges, A., Gander, A., Yu, D., Nasralla, D., Froghi, F., Iype, S., Davidson, B. R., Thorburn, D., Yona, S., Forns, X., & Maini, M. K.
- Affiliations
- University College London (GB)
- Liver Unit, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain 2
- Queen Mary University of London (GB)
- Hospital Clínic de Barcelona (ES)
- The Royal Free Hospital (GB)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Maini, Mala K.
- ORCID
- Pallett, Laura J.
- Burton, Alice R.
- Amin, Oliver E.
- Rodriguez-Tajes, Sergio
- Patel, Amit A.
- Zakeri, Nekisa
- Jeffery-Smith, Anna
- Swadling, Leo
- Schmidt, Nathalie M.
- Baiges, Anna
- Gander, Amir
- Yu, Dominic
- Nasralla, David
- Froghi, Farid
- Iype, Satheesh
- Davidson, Brian R.
- Thorburn, Douglas
- Yona, Simon
- Forns, Xavier
- Maini, Mala K.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2020-06-30
- Volume
- 217
- Issue
- 9
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC7478732
- OpenAlex
- W3039622640
- Cited by
- 134
- References
- 41
- Citations by year
- 2026: 22 · 2025: 19 · 2024: 25 · 2023: 21 · 2022: 27 · 2021: 15 · 2020: 5
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK
- Medical Research Foundation
- Instituto de Salud Carlos III (CM17/00015)
- Catalonian Society of Digestology
- Hospital Clínic de Barcelona
- ISCIII-Subdirección General de Evaluación (PI18/00079)
- Ministry of Economy and Competitiveness
- European Fund of Regional Development
- European Commission
- Secretaria d’Universitats I Recerca del Departament d’Economia i Coneixement (2017_SGR_1753)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- tissue-resident memory T cells, Kupffer cells, mononuclear phagocytes, liver allograft, HLA-mismatched transplantation, CX3CR1, CXCR3, organ transplantation
- MeSH terms
- Histocompatibility Testing, Humans, Immunologic Memory, Liver, Lymph Nodes, Phagocytes, Phenotype, Tissue Donors, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Myeloid Cells, Allografts
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 ›
Are you an author, or do you see a problem with this page? Request a review
