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The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease
Open accessAbstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage liver diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms of the immune system or their unidirectional interplay are commonly studied in MASLD. However, the bidirectional communication between innate and adaptive immune systems and its impact on MASLD remain insufficiently understood. Given that both innate and adaptive immune cells are indispensable for the development and progression of inflammation in MASLD, elucidating pathogenic contributions stemming from the bidirectional interplay between these two arms holds potential for development of novel therapeutics for MASLD. Here, we review the immune cell types and bidirectional pathways that influence the pathogenesis of MASLD and highlight potential pharmacologic approaches to combat MASLD based on current knowledge of this bidirectional crosstalk.
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“The roles of Tregs in MASLD and MASH remain unclear, with emerging evidence suggesting that their hepatic accumulation and functional relevance may vary depending on the disease model employed (Sawada et al. 2023).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Sawada et al. 2023
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Immunopathogenic mechanisms and immunoregulatory therapies in MASLD
He, Y., Chen, Y., Qian, S., van Der Merwe, S., Dhar, D., Brenner, D. A., & Tacke, F. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01307-5 · Cited by 81
Crudele, L., Matteis, C. D., Novielli, F., Buduo, E. D., Petruzzelli, S., Giorgi, A. D., Antonica, G., Berardi, E., & Moschetta, A. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00617-z · Cited by 62
“From a molecular perspective, hepatic immune cell function is reshaped during MASLD and contributes to disease pathogenesis [38] and natural killer T-cells may have a different role in males and females for MASLD development since they have been showed to protect against diet-induced…”
BackgroundCouteur, D. G. L., Ngu, M., Hunt, N. J., Brandon, A. E., Simpson, S. J., & Cogger, V. C. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01099-z · Cited by 73
Jee, Y.-M., Lee, J., & Ryu, T. (2025) · Biomedicines · doi:10.3390/biomedicines13051260 · Cited by 64
“Monoclonal antibodies targeting IL-6 or IL-6R have demonstrated efficacy in inflammatory diseases and are being explored for MASLD-related immune activation [27].”
InfluentialEnvisioning how to advance the MASH field
Allen, A. M., Younossi, Z. M., Diehl, A. M., Charlton, M., & Lazarus, J. V. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00938-9 · Cited by 64
Gao, X., Chen, T., Zhou, F., Sun, Y., Zhang, J., Li, X., Zhao, W., Li, Y., Shi, Y., Niu, K., et al. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02758-w · Cited by 55
“Second, the extremely low TyG-BMI may reflect the potential malnutrition or energy deficiency, which is associated with impaired immune function, decreased metabolic reserve and increased susceptibility to infection in MALD patients [42].”
Meyer, M., Schwärzler, J., Jukic, A., & Tilg, H. (2024) · Biomolecules · doi:10.3390/biom14040476 · Cited by 50
“Of note, the crosstalk between innate and adaptive immunity (as extensively reviewed elsewhere [5]), and also between immune-and non-immune cells such as hepatocytes, promotes liver inflammation in MASLD.”
BackgroundResearch progress on AMPK in the pathogenesis and treatment of MASLD
Feng, J., Li, M., TingTing, Y., Yi, X., & HaiNing, G. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1558041 · Cited by 36
“This pathological dialogue between hepatocytes and immune cells constitutes the core of the in fl ammatory response in MASH (41).”
Suresh, M. G., Mohamed, S., Geetha, H. S., Prabhu, S., Trivedi, N., Mehta, P. D., Damodaran, U. K., Brar, A., Sohal, A., Hatwal, J., et al. (2025) · Korean Circulation Journal · doi:10.4070/kcj.2025.0212 · Cited by 47
Liver-specific actions of GH and IGF1 that protect against MASLD
Kineman, R. D., del Río-Moreno, M., & Waxman, D. J. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01037-0 · Cited by 46
“Alterations in both the innate and adaptive immune systems affect the progression of MASLD 188 .”
Organoid-guided precision hepatology for metabolic liver disease
Osonoi, S., & Takebe, T. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.002 · Cited by 40
Implications of innate immune sexual dimorphism for MASLD pathogenesis and treatment
Booijink, R. S., Ramachandran, P., & Bansal, R. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.05.004 · Cited by 33
Acierno, C., Barletta, F., Caturano, A., Nevola, R., Sasso, F. C., Adinolfi, L. E., & Rinaldi, L. (2025) · Nutrients · doi:10.3390/nu17132229 · Cited by 33
“In particular, DAGs and ceramides promote endoplasmic reticulum (ER) stress and further mitochondrial ROS generation, reinforcing a dysfunctional redox environment [49].”
Zhang, S., Wang, R., Zhao, R., Lu, Y., Xu, M., Lin, X., Lan, R., Zhang, S., Tang, H., Fan, Q., et al. (2025) · Nutrients · doi:10.3390/nu17122013 · Cited by 28
Thyroid hormone receptor-beta agonists: new MASLD therapies on the horizon
Byrne, C. D., Targher, G., & Tilg, H. (2024) · Gut · doi:10.1136/gutjnl-2023-330596 · Cited by 32
Multiorgan crosstalk in MASLD/MASH: from hepatic pathogenesis to systemic complications
Bai, W., & Zhu, Z. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1720780 · Cited by 34
“Additionally, adaptive immune responses, including Th17 cell differentiation and autoantibody production, have been implicated in the progression of both MASH and extrahepatic autoimmune-like manifestations (95, 96).”
Romeo, M., Silvestrin, A., Senese, G., Nardo, F. D., Napolitano, C., Vaia, P., Coppola, A., Federico, P., Dallio, M., & Federico, A. (2025) · Biomedicines · doi:10.3390/biomedicines13082004 · Cited by 29
“Interestingly, obesity has been shown to shift NK cells toward an ILC1-like phenotype with reduced cytotoxicity, potentially promoting inflammation in MASH while offering protection against HCC, depending on the disease stage [56,85,86].”
InfluentialWei, Y., Jiang, Y., Zhu, J., Zhang, Z.-H., Li, M., Zheng, S., Wang, X.-Y., Sun, J., Li, C., Shi, W., et al. (2024) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2024.156127 · Cited by 25
Immunological dynamics in MASH: from landscape analysis to therapeutic intervention
Rabiu, L., Zhang, P., Afolabi, L. O., Saliu, M. A., Dabai, S. M., Suleiman, R. B., Gidado, K. I., Ige, M. A., Ibrahim, A., Zhang, G., et al. (2024) · Journal of Gastroenterology · doi:10.1007/s00535-024-02157-0 · Cited by 24
“These efforts aim to provide a more targeted approach to managing and treating MASLD [18].”
InfluentialThe multifaceted roles of B lymphocytes in metabolic dysfunction–associated steatotic liver disease
Li, H., & Xia, N. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1447391 · Cited by 23
Tsomidis, I., Tsakou, A., Voumvouraki, A., & Kouroumalis, E. (2026) · Biomedicines · doi:10.3390/biomedicines14010151 · Cited by 22
The PD-1/PD-L1 Axis in the Biology of MASLD
Pipitone, R. M., Lupo, G., Zito, R., Javed, A., Petta, S., Pennisi, G., & Grimaudo, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073671 · Cited by 20
“B7-1 and B7-2, expressed on APC, interact with the CD28 of T cells and induce the secretion of inflammatory cytokines, initiating inflammatory responses though the activation of CD8 + , CD4 + , and T Reg cells [91,92].”
Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation
Zhu, W., Hong, Y., Tong, Z., He, X., Li, Y., Wang, H., Gao, X., Song, P., Zhang, X., Wu, X., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101477 · Cited by 15
“7,8 To date, there are no approved drugs for MASH therapy in clinic.”
BackgroundMyeloid cells in chronic liver inflammation
Patseas, D., El-Masry, A., Liu, Z., Ramachandran, P., & Triantafyllou, E. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01324-4 · Cited by 20
“MASLD: The extent to which DCs contribute to MASLD has yet to be delineated, with data largely indicating contradictory conclusions [67, 72, 361].”
Chen, F., Li, S., Liu, M., Qian, C., Shang, Z., Xu, S., Jiang, W., & Tu, C. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05328-7 · Cited by 19
Cao, C., Liu, W., Guo, X., Weng, S., Chen, Y., Luo, Y., Wang, S., Zhu, B., Liu, Y., & Peng, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1460431 · Cited by 16
Zhou, J., & Han, J. H. (2024) · BMC Public Health · doi:10.1186/s12889-024-20161-0 · Cited by 17
“Inflammation is closely associated with the development of NAFLD, as it can lead to the destruction and fibrosis of liver tissues [42, 43].”
BackgroundLiu, Z., Wang, H., Liang, Y., Liu, M., Huang, Q., Wang, M., Zhou, J., Bu, Q., Zhou, H., & Lü, L. (2024) · Advanced Science · doi:10.1002/advs.202410880 · Cited by 16
The many pathways driving liver inflammation in MASH
Tilg, H., Adolph, T. E., Romeo, S., & Loomba, R. S. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.02.018 · Cited by 17
Yu, T., Fang, Z., Cheng, Y., Zhou, Y., Ji, Y., & Liu, C. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07253-0 · Cited by 14
“Concor-dant signals across bulk and single-cell datasets, together with in-vitro lipotoxicity assays and in-vivo HFD/MCD models, converge on a mitochondrial–immune axis in which COX6A1 heightens redox stress, perturbs lipid homeostasis, and shapes immune communication [59, 61].”
Zhang, J., Wang, W., Hou, X., Wu, J., Wang, Y., Fan, J., Zhang, Z., Yuan, Z., Sun, C., Lu, B., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1451908 · Cited by 14
Tan, Y., Hu, Y., Yang, Y., & Chu, H. (2025) · MedComm · doi:10.1002/mco2.70532 · Cited by 13
Kidney function evaluation in children and adolescents with obesity: a not-negligible need
Barlabà, A., Grella, C., Tammaro, M., Petrone, D., Guarino, S., del Giudice, E. M., Marzuillo, P., & Sessa, A. D. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05641-0 · Cited by 12
Kidney Damage in Pediatric Obesity: Insights from an Emerging Perspective
Forcina, G., Luciano, M., Frattolillo, V., Mori, S., Monaco, N., Guarino, S., Marzuillo, P., del Giudice, E. M., & Sessa, A. D. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13237025 · Cited by 13
“Despite some sparse and controversial evidence [38,43], the impact of overweight and obesity on pediatric kidney health has been well documented in recent years [8,9,11,44–47] (Table 1).”
Gut cannabinoid receptor 1 regulates alcohol binge-induced intestinal permeability
Maccioni, L., Dvorácskó, S., Godlewski, G., Çınar, R., Iyer, M. R., Gao, B., & Kunos, G. (2025) · eGastroenterology · doi:10.1136/egastro-2024-100173 · Cited by 12
Targeting THR-β for MASLD Treatment: Current Progression and Emerging Prospects
Li, J., Chen, R., Zhang, J., He, J., Wang, Y., & Li, Y. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03114 · Cited by 11
Acierno, C., Frontuto, M., Stefano, G. F. D., Erezanu, A., Limone, A., Morella, S., Picaro, F., Palazzo, D., & Gilio, M. (2025) · Biomedicines · doi:10.3390/biomedicines13102513 · Cited by 10
“…conditions such as MASLD (metabolic dysfunction-associated steatotic liver disease) and type 2 diabetes mellitus (T2DM), the metabolic regulation of immune cells undergoes profound disruptions, shifting them toward pro-inflammatory, senescent, and metabolically exhausted phenotypes [145].”
Xu, S., Zhang, Z., Zhou, Z., & Guo, J. (2026) · Biology · doi:10.3390/biology15020148 · Cited by 10
“This environment not only amplifies local inflammation but also provides the necessary priming signals for the activation, expansion, and phenotypic diversification of adaptive immune cells [72].”
Fan, L., Su, Y., Chen, Y., Xu, L., Huang, H., Lu, C., Peng, J., Sun, Y., & Jia, M. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1698297 · Cited by 10
“Triglyceride-cholesterol-body weight index, one composite indicator integrating TG, TC and BW, involves lipid metabolism disorder and energy surplus which are the core pathogenic factors of MASLD (27).”
Lu, Z., Yu, L., Bai, Y., Cui, Y., Shi, M., Li, Z., Li, X., Zhong, X., Ye, J., & Wei, C. (2025) · mSystems · doi:10.1128/msystems.00518-25 · Cited by 7
Growth Hormone, Hypothalamic Inflammation, and Aging
Velloso, L., & Donato, J. (2024) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes24032 · Cited by 8
Papadopoulos, G., Giannousi, E., Avdi, A. P., Velliou, R.-I., Nikolakopoulou, P., & Chatzigeorgiou, A. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1343806 · Cited by 8
Eid, R. A., Hamed, A. M., Elgendy, S. O., Orayj, K. M., Ibrahim, A. S., Hamied, A. M. A., Wahsh, E. A., Youssif, M., Rabea, H., Madney, Y. M., et al. (2025) · Metabolites · doi:10.3390/metabo16010025 · Cited by 9
Wang, Y., Chen, K., Yu, J., Tu, Y., Zhao, Y., Zhang, Y., Hu, Y., Yang, H. J., Yan, H., & Zheng, C. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-04018-3 · Cited by 8
Jia, S.-Z., Ye, X.-L., Kong, Y., Wang, Z.-X., & Wu, J. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000873 · Cited by 7
“In fi ltration and activation of immune cells may activate the innate and adaptive immune systems by secreting in fl ammatory cytokines, which in turn drive the development and progression of MASLD (9).”
Autoantibodies are associated with worse outcomes in MASLD
Sòria, A., Díaz, A., Iruzubieta, P., Martín‐Mateos, R., Salcedo-Allende, M. T., Jiménez-Masip, A., Fuster, C., Arias, M., Perna, C., Maimouni, C. E., et al. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101470 · Cited by 5
“47 A recent study demonstrated that the absence of speci fi c B-cell populations or impaired antibody secretion (IgMi mice) protects against hepatic steatosis, in fl ammation, and fi brosis in an MASLD mouse model.”
Huang, L.-Z., Ni, Z.-B., Yao, Q.-R., Huang, W.-F., Li, J., Wang, Y.-Q., & Zhang, J.-Y. (2025) · BMC Gastroenterology · doi:10.1186/s12876-024-03584-2 · Cited by 7
Cross-trait genomic modeling reveals the polygenic architecture and systemic impact of MASLD
Du, M., Yuan, H., Wu, T., Jiang, Y., Suo, C., Li, J., Zhang, T., Liu, Z., & Chen, X. (2026) · Science Advances · doi:10.1126/sciadv.aeb5665 · Cited by 7
“Some genes (e.g., EBF1 and COLEC11 ) also participate in immune and inflammatory regulation ( 51 , 52 ), suggesting shared pathways between metabolic and immune dysfunction in MASLD ( 53 ).”
Lambooij, J. M., Chavanelle, V., Vallier, M., van der Zande, H. J. P., Otero, Y. F., Otto, F., Schuurman, R., Joubioux, F. L., Maugard, T., Giera, M. A., et al. (2025) · npj gut and liver. · doi:10.1038/s44355-025-00033-z · Cited by 6
Li, W., Jiang, L.-N., Li, M.-L., Lin, C., Zhu, L., Zhao, B.-K., Liu, Y.-S., Li, Y., Jiang, Y.-Y., Liu, S.-H., et al. (2025) · Gastroenterology Report · doi:10.1093/gastro/goaf056 · Cited by 6
Licochalcone D ameliorates lipid metabolism in hepatocytes by modulating lipogenesis and autophagy.
Liou, C.-J., Wu, S.-J., Yang, H., Fang, L.-W., Cheng, S.-C., & Huang, W.-C. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176644 · Cited by 6
Luo, Z., Yan, S., Chao, Y., & Shen, M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28935 · Cited by 6
“…cell recruitment in NAFLD, can secrete large amounts of quantities of IL-6 and proteases, including myeloperoxidase, neutrophil elastase, and protease 3, enhancing the inflammatory environment, promoting ROS, and causing hepatocyte damage, thus contributing to the progression of NASLD[60 – 64].”
BackgroundLi, Y. C., Hu, Y., He, Y. M., Yang, Y., Xue, D., Xue, E., Jia, J., Zhang, W., & Wang, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1793092 · Cited by 4
“Overall, coordinated alterations in multiple metabolic signals may collectively reprogram the metabolic state of hepatic immune cells, favoring the maintenance of pro-in fl ammatory metabolic programs while reducing sensitivity to inhibitory regulatory cues (14, 50).”
Circulating histones as potential biomarkers of MASLD-MASH-HCC progression
Tsoneva, D. K., Búzová, D., Bianco, S. D., Braghini, M. R., Andolina, G., Liguori, A., Ambrosio, F. D., Urbani, A., Gasbarrini, A., Pompili, M., et al. (2025) · Epigenomics · doi:10.1080/17501911.2025.2611415 · Cited by 3
Li, J., Bai, X., Ni, W., Yin, S., Shi, J., Yang, Y., & Li, J. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115553 · Cited by 4
Bai, Y., Ju, J.-Y., Xie, R., Li, J., Zhao, X.-Y., Fang, X., Zhu, M., Lan, X., & Luo, H.-M. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115539 · Cited by 5
Engineering microfluidic human liver-islet crosstalk platform for recapitulating MASLD
Li, J., Wu, Z., Gan, J., Zhi, Y., Zhao, Y., & Li, L. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.165209 · Cited by 3
Yang, L., Li, W., Chen, Y., Ya, R., Qian, S., Liu, L., Hao, Y., Zai, Q., Xiao, P., Hwang, S., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.06.007 · Cited by 3
“Similarly, in pediatric patients with MASLD diagnosed by biopsy, approximately 50% of patients develop MASH, and 16% — 31% have advanced fibrosis 5,6 .”
Arai, J., Okumura, A., Kimoto, S., Sakamoto, K., Kitada, T., Kitano, R., Inoue, T., Nishimura, S., Inden, N., Muraki, Y., et al. (2025) · Hepatology International · doi:10.1007/s12072-025-10800-y · Cited by 4
“Notably, studies on immune responses in MASLD have traditionally focused on the role of innate immunity in disease development and progression [23].”
Ünal, K., Ibrahimkhanlı, L., Erol, M. E., Ibrahimkhanli, N., Altıntop, S. E., Cerit, M. N., Cerit, E. T., & Şendur, H. N. (2026) · International Journal of Tryptophan Research · doi:10.1177/11786469261423510 · Cited by 4
“2-4 The pathogenesis of MASLD is now primarily explained by the “multiple-hit” hypothesis, 5 which involves factors such as insulin resistance, hormones secreted by adipose tissue, nutritional factors, gut microbiota, and genetic factors.”
Gjurašin, B., Matotek, L. R., Marković, L. Š., & Papić, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168095 · Cited by 4
“Prior human studies in MASLD have shown increased baseline IL-6, IL-17A and TGF-β 1 which are associated with hepatic inflammation, insulin resistance, and fibrosis [26,27].”
Multifaceted Human Antigen R (HuR): A Key Player in Liver Metabolism and MASLD
Eppler, N., Jones, E., Ahamed, F., & Zhang, Y. (2025) · Livers · doi:10.3390/livers5030033 · Cited by 3
“These livers show increased infiltration of NKT cells and CD8 + T cells, immune subsets commonly associated with severe inflammation and fibrosis in MASLD [101,202,203].”
InfluentialSex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity
Brummer, C., Singer, K., Brand, A., Bruss, C., Renner, K., Herr, W., Pukrop, T., Dorn, C., Hellerbrand, C., Matos, C., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158234 · Cited by 4
X-chromosome gene dosage shapes MASLD beyond sex hormones
Jamalinia, M., Targher, G., & Lonardo, A. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2026.05.001 · Cited by 3
Liu, L., Duan, X., & Ju, B.-Z. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2025.1744299 · Cited by 3
Ye, B.-C., Teng, Y., Chen, Q.-Q., Zhang, J., Li, S., Dong, L., Xu, C., Qiao, X., & Miao, X. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-02220-x · Cited by 3
Lu, Y., Liu, L., Zhou, M., Zou, M., Ju, L., Yao, D., & Yao, M. (2025) · Liver International · doi:10.1111/liv.70421 · Cited by 3
“…from both HFD and HCC groups exhibited significant upregulation of immune system processes and leukocyte activation pathways, with prominent enrichment in lymphocyte activation modules, indicating a state of heightened immune activation dominated by lymphocytes in the MASLD environment [22, 23].”
Tram, V. T. N., Xuan, D. T. M., Nguyen, D. P. Q., Anuraga, G., & Ta, H. D. K. (2025) · Comput. Biol. Medicine · doi:10.1016/j.compbiomed.2025.110653 · Cited by 3
Vizioli, G., Nicoletti, A., Daniela, F., Funaro, B., Verme, L. Z. D., Ponziani, F. R., Zocco, M. A., Gasbarrini, A., & Gabrielli, M. (2025) · Applied Sciences · doi:10.3390/app15052279 · Cited by 1
Onisor, D., Roiban, A. L., & Cernea, S. (2024) · Medicina · doi:10.3390/medicina60122091 · Cited by 3
Lee, S. E., Jo, M. G., Park, S. W., Kim, H. J., Yun, S. P., & Kim, J.-W. (2026) · Animal Cells and Systems · doi:10.1080/19768354.2026.2630463 · Cited by 2
“The roles of Tregs in MASLD and MASH remain unclear, with emerging evidence suggesting that their hepatic accumulation and functional relevance may vary depending on the disease model employed (Sawada et al. 2023).”
Li, S., Lambertucci, F., Montégut, L., Martins, I., Pol, J. G., Piacentini, M., Maiuri, M. C., & Kroemer, G. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08148-0 · Cited by 3
“Its decisions ripple outward, in fl uencing the behavior of virtually every organ — dictating energy supply, affecting nutrient absorption, calibrating biosynthesis, orchestrating detoxi fi cation, and modulating immune activity [3, 4].”
Pan-immune-inflammation value and mortality in the US adult MASLD: a nonlinear NHANES analysis
Zhou, Q., Xue, J., & Hao, L. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-04064-x · Cited by 2
Jin, Z., Cao, J., Liu, Z.-X., Gao, M., & Liu, H.-L. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100366 · Cited by 2
“Hepatic immune cell populations reshape during MASH and contribute to disease pathogenesis [1].”
InfluentialYe, D., Wang, J., Shi, J., Ma, Y., Chen, J., Hu, X., & Bao, Z. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02245-3 · Cited by 2
“Recent investigations have highlighted the role of immune mediators from both resident liver parenchymal cells and a cohort of resident and infiltrating immune cells in precipitating the activation of innate and adaptive immune responses, thereby promoting the onset and progression of MASLD [30].”
BackgroundSawada, K., Oates, J. R., Kimura, M., Stankiewicz, T. E., Eom, J., Alarcon, P. C., Chung, H., Damen, M. S. M. A., Ulanowicz, C. J., Wayland, J. L., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.08.018
Self-citationMakri, E. S., & Pοlyzos, S. A. (2026) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2026.46 · Cited by 1
Vecchio, C., Sheferaw, A. N., Kivumbi, E., Stoppa, I., Pantham, D., Christaki, F., Provera, A., Dianzani, U., & Sutti, S. (2026) · Inflammation · doi:10.1007/s10753-026-02545-z · Cited by 1
“…stages of disease, these cells may exert regulatory functions, whereas in more advanced stages, they acquire a pro-inflammatory and pro-fibrotic phenotype, releasing cytokines and chemokines that promote the recruitment of neutrophils and macrophages and activate hepatic stellate cells [161–163].”
Chng, W. Q., Liew, J. J., Liew, C. F., Muthiah, M., Zheng, M., & Oon, H. H. B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1831174 · Cited by 1
“In psoriasis, Th17 cells are activated by the IL-23 pathway through myeloid dendritic cells 10 .”
InfluentialYou, X., Zhang, L., Fang, K., Huang, H.-F., Hu, Y., Gu, M., Qu, Q., Xue, F., Huang, S.-X., Wu, Z., et al. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102297 · Cited by 1
Boateng, S., Nguefang, G., Mapouka, M., Lawal, R., Gyabaah, S., Nwatamole, B., Kasar, A., Adatsi, S., & Njei, B. (2026) · Gastro Hep Advances · doi:10.1016/j.gastha.2026.101030 · Cited by 1
Effects and Mechanisms of Stevioside on Metabolic Dysfunction‐Associated Steatotic Liver Disease
Li, K., Zhang, C., Kang, L., Mu, Y., Li, Z., Zhang, J. I.-X., & Li, G. H. (2026) · Food Science & Nutrition · doi:10.1002/fsn3.71945 · Cited by 1
Ambient temperature regulates CD4+ T cell tonic T cell receptor signaling and responsiveness
Sawada, K., Eom, J., Mahoney-Sutherland, B. A., Stankiewicz, T. E., Oates, J. R., Giles, D. A., Alarcon, P. C., Damen, M. S. M. A., Cannata, A., Hargis, J., et al. (2026) · iScience · doi:10.1016/j.isci.2026.115801 · Cited by 2
“To interrogate this relationship in MASLD, WT mice were fed a high-fat diet for 20 weeks in either Tn-or Ts-conditions (Figure 5A).”
InfluentialSelf-citationRomeo, M., Basile, C., Martinelli, G., Nardo, F. D., Napolitano, C., Gregorio, A. D., Vaia, P., Puorto, L. D., Indipendente, M., Federico, A., et al. (2026) · Cancers · doi:10.3390/cancers18081316 · Cited by 1
Nash, M. J., Nelson, B. N., McGuckin, M. M., Janssen, R. C., Jones, K. L., Al‐Juboori, S. I., Dobrinskikh, E., Kievit, P., Aagaard, K. M., McCurdy, C. E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.06.697995 · Cited by 1
“Macrophage activation promotes MASLD progression in adults 34 .”
MASLD: Lipotoxicity and Imaging Parallels from Liver Steatosis to Kidney Injury
Săndulescu, S. M., Ghiga, D. Ș., Tudoraşcu, D. R., Săndulescu, L., Mită, A., Urhuț, M. C., & Taisescu, C. I. (2025) · Life · doi:10.3390/life15121805 · Cited by 3
“Beyond the innate cascade detailed above, adaptive immunity through dendritic cells, natural killer cells, and T and B lymphocytes also contributes, and its bidirectional crosstalk with innate immunity in MASLD has been recently reviewed [65].”
Lee, J.-D., Kwak, J., Kim, M.-H., Lee, S.-H., Cho, J.-H., Lim, D.-J., Lee, J.-M., Chang, S.-A., & Kim, H. (2025) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2025.006 · Cited by 1
“The hypothesized association between MASLD and thyroid cancer could be mediated through mechanisms such as chronic inflammation, insulin resistance, and altered adipokine levels, which are key features of metabolic dysfunction [8].”
Zhang, F., Liu, L.-G., & Li, W.-J. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01724-6 · Cited by 1
Huang, Z., Chen, J., Liu, S., Xiang, X., Long, Y., Tan, P., & Fu, W. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s497737 · Cited by 1
“8,9 Hepatic immune cells exhibit diversity in the steady state and continue to evolve during NASH, directly impacting the disease’s severity.”
Ren, M., Ren, J., Zheng, J., Sha, X.-T., Lin, Y., & Wu, F.-H. (2024) · Antioxidants · doi:10.3390/antiox13091136 · Cited by 1
“Fatty liver patients with obesity, overweight, insulin resistance, dyslipidemia, and other metabolic factors can be diagnosed as MASLD [1].”
BackgroundHu, X., Meng, F., Zhou, W., Li, S., 高玉杰, Zhang, Y., Zhang, J., Kong, L., Liu, G., 石晓红, et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1849699
Glutamine metabolism keeps pathogenic hepatic CD4+ T cells in check.
Wang, H.-G., Hakeem, A., & Revelo, X. S. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.09.004
He, Y., Ma, T., 邢邯英, Cao, X., Song, F., Pan, Y., & Luping, R. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179418
Anouti, A., Danpanichkul, P., Dahshi, H., Rady, E. D., Pandurangi, S., Hassan, S., Aqul, A., Kerr, T. A., Kwon, Y. K., Patel, M. S., et al. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102456
Zhong, Q.-Q., Lyu, W., Li, J.-Y., Song, Y.-M., Huang, Y.-X., Wang, C.-B., & Ji, J.-L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1963310
Onoiu, A.-I., González-Serrano, S., Cambra-Cortés, V., Jiménez-Franco, A., Guilarte, C., Peña, K. B., Riu, F., Camps, J., Joven, J., & Parada, D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1816648
Cyclo(Val-Pro) and cyclo(Phe-Phe) alleviate MASLD via distinct CCR2- and ADCY7-associated pathways.
Zhou, J., Jin, H.-J., Zheng, Y.-F., Ding, K.-Y., Long, Y., Yu, C.-J., Zhang, Y.-R., Zhuge, F., Chen, M.-H., Fu, Z.-W., et al. (2026) · Life Science · doi:10.1016/j.lfs.2026.124669
Chen, Y., Lin, Z.-H., Niu, Y., Zheng, Q.-Q., Chen, M.-M., & Gao, P. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158839
Qu, J., Sheng, X., Ma, Y., Li, R., Wang, Y., Jiang, X., Qian, D., Wang, P., Yi, J., Wen, L., et al. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.120708
Bai, H., Fan, G., Deng, B., Liu, Y., Zhang, P., Cao, X., & Li, Y. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117306
Metadata
- Authors
- Sawada, K., Chung, H., Softic, S., Moreno-Fernandez, M. E., & Divanovic, S.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Kentucky (US)
- Corresponding author
- Divanovic, Senad
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 35
- Issue
- 11
- Pages
- 1852-1871
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC10680147
- OpenAlex
- W4388452323
- Cited by
- 139
- References
- 316
- Citations by year
- 2026: 56 · 2025: 51 · 2024: 32
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (17POST33650045)
- CCHMC
- Cincinnati Children’s Research Foundation
- National Institutes of Health (R01DK099222)
- U.S. Department of Defense (W81XWH2010392)
- American Diabetes Association (1-18-IBS-100)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, innate immunity, adaptive immunity, liver inflammation, immune cell types, therapeutic target
- MeSH terms
- Fatty Liver, Humans, Inflammation, Metabolic Diseases, Pancreas, Risk Factors
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