bims-maitce 2025-06-15 papers

Issue of 2025–06–15
three papers selected by
Andy E. Hogan, Maynooth University

Int Immunopharmacol. 2025 Jun 10. pii: S1567-5769(25)01059-8. [Epub ahead of print]161 115069

Mucosal-associated invariant T cells in diabetes mellitus: Protective or destructive?

Mahvash Sadeghi, Sajad Dehnavi, Amir Mohammad Amiri, Alexandra E Butler, Amirhossein Sahebkar.

Diabetes mellitus (DM) is a chronic metabolic condition that can be categorized into two major subsets, type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Recently, studies in diabetic patients and animal models have demonstrated the dual role of mucosal-associated invariant T (MAIT) cells in the context of diabetes mellitus. MAIT cell populations are altered in T1DM, exhibiting a reduced frequency and exhausted profile characterized by reduced cytokine production. These alterations correlate with disease progression and may contribute to destruction of β-cells. Conversely, in T2DM, MAIT cells are often reduced and exhibit a pro-inflammatory phenotype related to obesity and insulin resistance. Understanding the precise role of MAIT cells in DM may provide insight into innovative therapeutic approaches aimed at modulating their function to enhance disease outcomes. This review highlights the characteristics, function and activation of MAIT cells. We also review the in vivo and in vitro studies on the role of MAIT cells in T1DM and T2DM. Finally, we focus on the therapeutic applications of these cells for the management of DM patients.

Keywords: Autoimmune diseases; Diabetes mellitus; Mucosal-associated invariant T (MAIT) cells; Type 1 diabetes mellitus (T1DM); Type 2 diabetes mellitus (T2DM)

DOI: https://doi.org/10.1016/j.intimp.2025.115069

Cell Mol Immunol. 2025 Jun 11.

Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

Deniz Seyhan, Manon Allaire, Yaojie Fu, Filomena Conti, Xin Wei Wang, Bin Gao, Fouad Lafdil.

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

Keywords: Hepatocellular carcinoma; Immune microenvironment; Immunotherapy.

DOI: https://doi.org/10.1038/s41423-025-01308-4

Front Immunol. 2025 ;16 1567306

Dynamic alterations of circulating lymphocytes during the trajectory of Hantaan virus-induced hemorrhagic fever with renal syndrome.

Lin Su, Shuangjuan Liu, Lei Shi, Yuan Cheng, Juanjuan Gao, Ruirui Guo, Yinli He, Linpei Zhang, Tianyan Chen, Jinsong Hu, Xiaojiao Li, Yawen Wang.

Introduction: Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease with high mortality. Almost 90% of global cases of HFRS are induced by Hantaan virus (HTNV) infection. Although lymphocyte dysfunction is a critical factor in HFRS progression, the specific immune dynamics of HTNV remain unexplored, and current analyses predominantly depend on single-time point sampling. Therefore, comprehensive longitudinal studies are needed to characterize circulating lymphocyte dynamics during HTNV-induced HFRS progression.
Methods: In this study, we conducted a flow cytometric analysis of circulating lymphocytes in 39 patients with HTNV-induced HFRS across different clinical phases. The analysis encompassed conventional T cells, unconventional T cells, B cells, NK cells and their respective repertoires.
Results and Discussion: Here, we revealed phase-specific immune patterns: CD8+ T, CD8+ Tems, and activated CD8+ T, MAIT and NKT cells peaked during febrile/oliguric phases before declining in polyuria/recovery, while CD4+ T and MAIT cells showed inverse fluctuation patterns. Higher frequencies of CD8+ Tem, B, and CD56dim NK cells during the febrile phase correlated with severe disease, enabling early risk stratification. Lower CD4+ Tcm levels in the oliguric phase marked progression to severe HFRS, indicating potential therapeutic strategies aimed at enhancing CD4+ Tcm generation or inhibiting effector differentiation. Additionally, CD38 and CD161 expression predicted specific lymphocyte subset dynamics, offering novel biomarkers for immunomodulatory strategies. Our study thus provides the first comprehensive atlas of lymphocyte evolution in HTNV-induced HFRS, connecting immune dysregulation with clinical outcomes.

Keywords: HFRS; HTNV; biomarkers; dynamic alterations; lymphocyte subsets

DOI: https://doi.org/10.3389/fimmu.2025.1567306