Adaptive immunity: an emerging player in the progression of NAFLD
Open accessAbstract
In the past decade, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease and cirrhosis, as well as an important risk factor for hepatocellular carcinoma (HCC). NAFLD encompasses a spectrum of liver lesions, including simple steatosis, steatohepatitis and fibrosis. Although steatosis is often harmless, the lobular inflammation that characterizes nonalcoholic steatohepatitis (NASH) is considered a driving force in the progression of NAFLD. The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. However, increasing evidence points to the role of adaptive immunity as an additional factor promoting liver inflammation. This Review discusses data regarding the role of B cells and T cells in sustaining the progression of NASH to fibrosis and HCC, along with the findings that antigens originating from oxidative stress act as a trigger for immune responses. We also highlight the mechanisms affecting liver immune tolerance in the setting of steatohepatitis that favour lymphocyte activation. Finally, we analyse emerging evidence concerning the possible application of immune modulating treatments in NASH therapy.
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In MASLD, the hepatic immunological equilibrium is perturbed, resulting in chronic low-grade inflammation and inappropriate activation of innate and adaptive immune responses.
“In MASLD, this finely tuned immunological equilibrium is perturbed, resulting in chronic low-grade inflammation and inappropriate activation of both innate and adaptive immune responses (Shrestha et al. 2025; Sutti and Albano 2020).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Sutti and Albano 2020
The Introduction and ‘Innate and adaptive cell interplay’ sections describe innate and adaptive immune responses contributing to liver inflammation, while ‘Mechanisms promoting adaptive immunity’ describes disruption of the liver’s normally tolerogenic environment. The review centers these findings on NASH, however, and ‘Innate immunity in NASH’ notes that only a fraction of patients with steatosis develop hepatic inflammation. It therefore does not support presenting chronic inflammation and activation of both responses as occurring throughout MASLD. (LLM, conf=0.85)
Experimental — accuracy not yet measuredTregs exhibit increased susceptibility to apoptosis in MASH.
“Tregs consistently exhibit an increased susceptibility to apoptosis in MASH (Sutti and Albano 2020).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Sutti and Albano 2020
The “Regulatory T cells in the liver” section says Treg cells in fatty livers are more susceptible to apoptosis in response to oxidative stress than those in nonfatty livers. It does not establish that this occurs consistently in MASH specifically, or without the oxidative-stress condition. (LLM, conf=0.85)
Experimental — accuracy not yet measuredImmune dysregulation critically contributes to MASLD pathogenesis.
“growing evidence has highlighted the critical contribution of immune dysregulation to its pathogenesis.”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Sutti and Albano 2020
Recent evidence indicates that adaptive immunity plays an essential role in the progression of NASH, fibrosis, and HCC.
“However, recent evidence indicates that adaptive immunity plays an essential role in the progression of NASH, fibrosis, and HCC.( 6 )”
From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [6]
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ATVB Distinguished Scientist Award
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- Authors
- Sutti, S., & Albano, E.
- Affiliations
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Corresponding author
- Albano, Emanuele
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2019-10-11
- Volume
- 17
- Issue
- 2
- Pages
- 81-92
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC7222953
- OpenAlex
- W2979371456
- Cited by
- 374
- References
- 137
- Citations by year
- 2026: 35 · 2025: 42 · 2024: 67 · 2023: 70 · 2022: 75 · 2021: 55 · 2020: 27 · 2019: 1 · 2017: 1
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondazione Cariplo (2011-0470)
- Ministero dell’Istruzione, dell’Università e della Ricerca (FAR 2015)
- Topics
- Health Sciences › Medicine › Epidemiology › 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, nonalcoholic steatohepatitis, adaptive immunity, B cells, T cells, liver inflammation, liver fibrosis, hepatocellular carcinoma, immune tolerance, immunomodulatory therapy, disease progression
- MeSH terms
- B-Lymphocytes, Carcinoma, Hepatocellular, Humans, Immune Tolerance, Immunity, Innate, Liver Cirrhosis, Liver Neoplasms, T-Lymphocytes, Oxidative Stress, Disease Progression, Natural Killer T-Cells, Adaptive Immunity, Non-alcoholic Fatty Liver Disease
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