bims-maitce 2026-09-06 papers

Issue of 2026–09–06
five papers selected by
Andy E. Hogan, Maynooth University

Cell Immunol. 2026 Aug 26. pii: S0008-8749(26)00093-6. [Epub ahead of print]428-429 105152

TNF and CD107a-dominated enhanced effector responses of CD8+ MAIT cells to Escherichia coli stimulation in patients with aplastic anemia.

Qiuzhi Qin, Yuping Zhang, Shujuan Wu, Sini Fan, Xiaoqing He, Xueqin Li, Wei Bian, Yangqiu Li, Bo Li.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that respond rapidly to microbial metabolites presented by MR1. Patients with aplastic anemia (AA) are prone to bacterial and fungal infections, but the MR1-related effector responses of MAIT cells in AA remain unclear.
METHODS: Peripheral blood mononuclear cells from 27 patients with AA and 29 healthy individuals were stimulated with fixed Escherichia coli for 2, 3, 6, or 12 h, with or without MR1 blockade. CD8+ MAIT cell activation, cytokine production, degranulation, CD69 expression, and polyfunctional profiles were assessed by flow cytometry.
RESULTS: CD8+ MAIT cells from patients with AA showed higher CD69 expression under unstimulated conditions, suggesting a basal activation state. After fixed E. coli stimulation, CD8+ MAIT cells from patients with AA displayed enhanced early effector responses compared with those from healthy individuals, characterized by increased TNF production, CD107a expression, and polyfunctional subset frequencies, particularly CD107a+TNF+ populations. These enhanced responses were most pronounced at 6 h after stimulation. MR1 blockade markedly reduced E. coli-induced cytokine production and CD107a expression in CD8+ MAIT cells, supporting an important contribution of MR1-dependent signaling to these responses.
CONCLUSIONS: In patients with AA, CD8+ MAIT cells display markedly enhanced effector functions and polyfunctional responses upon E. coli stimulation. These findings indicate that riboflavin metabolism-related bacterial infection in patients with AA can induce functional disorders of CD8+ MAIT cells via the MR1-TCR pathway.

Keywords: Aplastic anemia; CD107a; CD8(+) MAIT cells; Escherichia coli; MR1; TNF

DOI: https://doi.org/10.1016/j.cellimm.2026.105152

Med. 2026 Sep 02. pii: S2666-6340(26)00275-8. [Epub ahead of print] 101272

Adoptive MAIT cell therapy for liver cancer enhanced by multimodal modulation of immune receptors and checkpoints.

Yan-Ruide Li, Xinyuan Shen, Yichen Zhu, Yuning Chen, Jie Huang, Shelby Yeh, Thomas Yuen, Coral L Clune, Paulina Dominguez-Vela, Shreya Gumate, Vatche G Agopian, Lili Yang.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that recognize riboflavin-derived metabolites presented by the monomorphic major histocompatibility complex (MHC)-class I-related molecule MR1. MAIT cells are highly enriched in the human liver and are increasingly implicated in liver cancer immunity, yet their antitumor potential and therapeutic applicability remain incompletely defined.
METHODS: Here, we profiled MAIT cells derived from peripheral blood of healthy donors and patients with hepatocellular carcinoma, revealing disease-associated phenotypic alterations marked by immune checkpoint dysregulation. To address current therapeutic limitations, we developed a robust ex vivo expansion platform capable of generating MAIT cells with high yield, purity, and potent cytotoxic function. Using multiple human liver cancer subcutaneous and orthotopic xenograft mouse models, we demonstrate that adoptively transferred MAIT cells mediate effective tumor targeting and killing in vivo.
FINDINGS: Mechanistically, MAIT cell antitumor activity is driven by both T cell receptor (TCR)-dependent recognition and natural killer receptor (NKR)-mediated cytotoxicity and is further enhanced by antigen stimulation; cytokine receptor signaling, particularly via interleukin (IL)-15; and immune checkpoint modulation involving programmed cell death protein 1 (PD-1) and T cell immunoglobulin and ITIM domain (TIGIT). In addition, MAIT cells demonstrated a favorable safety profile, with no evidence of liver toxicity observed in xenograft mouse models.
CONCLUSIONS: Together, these findings establish MAIT cells as functional antitumor effectors in liver cancer and provide a mechanistic and translational framework for adoptive MAIT cell therapy enhanced by multimodal modulation of immune receptors and checkpoints.
FUNDING: Major funding was provided by the California Institute for Regenerative Medicine (CIRM).

Keywords: 5-OP-RU; MAIT; PD-1; TIGIT; cancer immunotherapy; cytokine receptor; hepatocellular carcinoma; immune checkpoint; liver cancer; mucosal-associated invariant T cell; pre-clinical research

DOI: https://doi.org/10.1016/j.medj.2026.101272

Front Neurol. 2026 ;17 1900084

Longitudinal immune profiling demonstrates persistent MAIT cell reduction and temporal cytokine alterations after aneurysmal subarachnoid hemorrhage.

Akos Merei, Noemi Balazs, Brotzki Da Costa Chayeen, Peter Engelmann, Timea Berki, Szabina Erdő-Bonyár, Diana Simon, Tihamer Molnar, Csaba Olah, Peter Csecsei.

Background: Neuroinflammation and systemic immune dysregulation are increasingly recognized as key contributors to secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). However, the temporal relationship between circulating cytokine responses and innate-like lymphocyte populations, particularly mucosal-associated invariant T (MAIT) cells, remains poorly characterized.
Methods: In this prospective observational study, peripheral blood cytokine profiles were longitudinally analyzed in 48 patients with aSAH on days 1, 5, and 9 after ictus and compared with healthy controls. Serum concentrations of IL-6, IL-7, IL-12p40, IL-12p70, IL-15, IL-17A, IL-18, IL-22, IP-10, and CXCL-9 were measured using multiplex immunoassay. Flow cytometric immunophenotyping was performed in a subgroup of 16 patients to evaluate MAIT cells, NK cells, γδ T cells, iNKT cells, and NKT-like cells. Associations between immune parameters and 3-month functional outcome were also assessed.
Results: Patients with aSAH demonstrated persistently elevated IL-6, IL-18, and IL-15 levels across all examined time points, while IL-7, IL-12p40, IP-10, and CXCL-9 showed delayed increases during the subacute phase. IL-6 and IL-15 concentrations were significantly higher in patients with unfavorable outcome, whereas IL-22 levels were increased in patients with favorable recovery. However, these associations were not independent of disease severity after adjustment for WFNS score and age. Flow cytometry revealed a persistent reduction in circulating MAIT-cell frequencies following aSAH, while other innate-like lymphocyte populations remained largely unchanged. DN MAIT-cell frequencies demonstrated significant negative correlations with circulating IL-18 levels across all examined time points.
Conclusion: aSAH is associated with sustained systemic inflammatory activation and selective alterations of MAIT-cell populations. Although several cytokines were associated with functional outcome in univariate analyses, these associations were attenuated after adjustment for WFNS score and age, suggesting that they primarily reflect disease severity rather than independent prognostic effects. The observed relationship between MAIT-cell dysregulation and IL-18-associated inflammation provides further evidence of altered innate-like immune responses following aSAH.

Keywords: aneurysmal subarachnoid hemorrhage; inflammation; interleukins; mucosal-associated invariant T cells; outcome

DOI: https://doi.org/10.3389/fneur.2026.1900084

J Inflamm Res. 2026 ;19 564229

Alleviation of Chitin- and Ovalbumin-Induced Steroid-Resistant Eosinophilic Airway Inflammation Associated with NLRP3 Axis Inhibition in a Mouse Model.

Shoko Ueda Matsuda, Norihiro Harada, Sonoko Harada, Hitoshi Sasano, Takayasu Nishimaki, Yoshihiko Sato, Sumiko Abe, Yuuki Sandhu, Yuki Tanabe, Tomohito Takeshige, Asako Chiba, Hisaya Akiba, Sachiko Miyake, Kazuhisa Takahashi.

Background: Steroid resistance complicates asthma management in some patients. However, its mechanisms remain unclear. In our previous study, we developed a novel mouse model using inhaled chitin-a pathogen-associated molecular pattern-which, when combined with ovalbumin (OVA), induces steroid-resistant airway inflammation and airway hyperresponsiveness. This study aimed to investigate the specific intrapulmonary lymphocyte populations implicated in the pathogenesis of chitin-induced steroid-resistant asthma and evaluate the therapeutic potential of NLRP3 inflammasome inhibition in reversing this resistance.
Methods: BALB/c mice were intranasally challenged with OVA alone or OVA combined with chitin, with or without dexamethasone (DEX). Lung cells were harvested 24 h after the final challenge and analyzed using flow cytometry.
Results: Co-stimulation with OVA and chitin significantly increased the total number of lung cells, eosinophils, IL-17-producing Th cells, ILC2s, invariant natural killer T (iNKT) cells, and mucosal-associated invariant T (MAIT) cells. Although DEX effectively suppressed these immune responses induced by OVA alone, it could not inhibit responses induced by OVA/chitin. Notably, administering an NLRP3 inflammasome inhibitor restored steroid sensitivity, reducing eosinophilic inflammation and dampening the number of Th17, ILC2s, iNKT, and MAIT cells.
Conclusion: Our findings suggest that the NLRP3 axis may play a role in chitin-induced steroid-resistant eosinophilic airway inflammation. Targeting this axis, together with corticosteroids, could be a potential therapeutic strategy.

Keywords: NLRP3 inflammasome; airway inflammation; chitin; steroid-resistant asthma; type 2 inflammation

DOI: https://doi.org/10.2147/JIR.S564229

Front Med (Lausanne). 2026 ;13 1899423

Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.

Fukang Mao, Keji Shan.

The liver serves the triple functions of metabolism, detoxification, and immune surveillance. Its unique immune microenvironment is shaped by continuous exposure to gut-derived antigens, pathogen-associated molecular patterns (PAMPs), and metabolites arriving via the portal vein, necessitating a delicate equilibrium between immune tolerance and effector activation. This equilibrium relies on the coordinated activities of diverse liver-resident immune cell populations-including Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), dendritic cells (DCs), tissue-resident memory T cells (TRM), innate-like T cells, including mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδ T cells, innate lymphoid cells (ILCs, encompassing conventional NK cells and helper ILC subsets), and neutrophils. With advancing age and chronic injury, these resident immune cell populations undergo profound senescence-associated phenotypic reprogramming that is spatially organized along the portal-to-central axis of the hepatic lobule. Key mechanisms include: telomere dysfunction and DNA damage accumulation driving persistent activation of p53/p21 and p16/Rb pathways; mitochondrial dysfunction with mitochondrial DNA (mtDNA) leakage fueling the senescence-associated secretory phenotype (SASP) via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; epigenetic age acceleration, including genome-wide H3K27me3 heterochromatinization; and metabolic reprogramming toward glycolysis and lipid accumulation. This review proposes a "spatial niche remodeling" framework to integrate these cell-intrinsic senescence programs with their lobular context, intercellular communication network rewiring, and pathogenic roles across the spectrum of chronic liver disease-from steatosis through steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. We critically evaluate emerging senotherapeutic strategies targeting specific liver-resident immune cell subsets, discuss the barriers to clinical translation, and identify priority areas for future investigation, including the application of spatial multi-omics, humanized models, and epigenetic clock-guided clinical trials.

Keywords: Kupffer cells; cellular senescence; chronic liver disease; liver-resident immune cells; senescence-associated secretory phenotype; single-cell transcriptomics; spatial niche remodeling; tissue-resident memory T cells

DOI: https://doi.org/10.3389/fmed.2026.1899423