AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity

Leite, Jefferson Antônio; Menezes, Luísa; Martins, Eloisa; Rodrigues, Tamara Silva; Tavares, Lucas; Ebering, Anna; Schelmbauer, Carsten; Martelossi Cebinelli, Guilherme C.; Zinina, Valeriya; Golden, Artemiy; Soshnikova, Natalia; Zamboni, Dario S.; Cunha, Fernando Q.; Huber, Magdalena; Silva, João Santana; Waisman, Ari; Carlos, Daniela; Saraiva Câmara, Niels Olsen

doi:10.1016/j.isci.2023.108134

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…We found that the frequency of cluster 0 was increased in mice injected with pro-inflam Macs, while the frequency of cluster 1 and cluster 2 were significantly decreased (Figure 6A). In addition to genes associated with Th17 cells (IL-17a, IL17f, Rora, Il1r1, TNF) (Wu et al, 2019;Leite et al, 2023), cluster 0 also exhibits high expression of genes associated with memory phenotype (Cxcr6, S100a4, CD44) (Schroeder et al, 2023;Bieberich et al, 2021), suggesting that cluster 0 was the memory-like Th17 cells (Figure 6A, 6C). Cluster 1 exhibits high expression of genes associated with immunoregulation (Lef1, Tcf7, Ccr7) (Qiu et al, 2022;Sekine et al, 2020); Cluster 2 exhibits high expression of genes associated with immunosuppression (Gata3, GITR, CD28), suggesting that cluster 1 and 2 were T cells with immunosuppressive function (Esensten et al, 2016;Pai et al, 2023) (Figure 6A, 6C).…”

Section: Pro-inflam Macs Induced the Memory-like Th17 Cells Which Was...mentioning

confidence: 99%

WITHDRAWN: Unveiling the Crucial Role of Pro-inflammatory Macrophages in the Immune Network Imbalance of the maternal-fetal interface with Preeclampsia

Fei,

Lu,

Shi

et al. 2024

Preprint

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Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, Cytometry by time of flight (CyTOF) indicated that the frequencies of memory-like Th17 cells (CD45RA-CCR7+IL-17A+CD4+), memory-like CD8+T cells (CD45RA-CCR7+CD38+pAKTmidCD127low) and pro-inflam Macs (CD206-CD163-CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of CD69hiHeliosmidCD127midγδT cells, anti-inflam Macs (CD206+CD163-CD86midCD33+HLA-DR+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of NP, but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F480+CD206-pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+Th17 cells via IGF1-IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+gMDSCs at the maternal-fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.

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Section: Pro-inflam Macs Induced the Memory-like Th17 Cells Which Was...mentioning

confidence: 99%

WITHDRAWN: Unveiling the Crucial Role of Pro-inflammatory Macrophages in the Immune Network Imbalance of the maternal-fetal interface with Preeclampsia

Fei,

Lu,

Shi

et al. 2024

Preprint

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Impact of AIM2 on HNSCC Development

Reinartz,

Escamilla-River,

Tribble

et al. 2024

Preprint

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Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of head and neck cancers. HNSCC development is linked to chronic inflammation, while established HNSCC tumors are often immune suppressive. However, both occur through mechanisms that are not fully understood. The cytosolic double-stranded DNA sensor Absent in Melanoma 2 (AIM2) is an inflammasome forming protein that also has inflammasome-distinct roles in restricting tumorigenesis by limited PI3K signaling. Here, we used an experimental mouse model of HNSCC, involving treatment of wild type (WT) and Aim2-/- mice with the carcinogen 4NQO in drinking water. Compared to WT mice, 4NQO-treated Aim2-/- mice exhibited larger tumor sizes and increased tissue dysplasia. 4NQO-treated wild type and Aim2-/- mice displayed similar tongue Il6, Tnf, Il1b, Il12, and Il10 expression and no consistent differences in PI3K or inflammasome activation, suggesting AIM2 may not regulate these factors during HNSCC. Instead, Ifng and Irf1 was elevated in 4NQO-treated Aim2-/- mice, suggesting AIM2 restricts IFNγ. In line with this, RNA-sequencing of total tongue RNA from 4NQO-treated mice revealed Aim2-/- mice had enhanced expression of genes related to the MHC protein complex, cell killing, and T cell activation compared to wild type mice. In addition, we observed increased macrophage infiltration into the tongue epithelium of 4NQO-treated Aim2-/- mice. Lastly, using Aim2-/-/Rag1-/--double deficient animals, we found that the adaptive immune compartment was necessary for the enhanced tumorigenesis during AIM2 deficiency. Taken together, these findings suggest AIM2 limits the progression of oral tumor development partially through regulating IFNγ and adaptive immune responses.

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The role of AIM2 in inflammation and tumors

Yu,

Zheng,

Sui

et al. 2024

Front. Immunol.

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Absent in melanoma 2 (AIM2) serves as an intracellular nucleic acid sensor that predominantly detects double-stranded DNA (dsDNA) within the cells. This detection initiates the assembly of inflammasome and activates the inflammasome signaling cascade, resulting in the production of inflammatory mediators and the cleavage of Gasdermins. Consequently, these processes culminate in inflammatory responses and pyroptotic cell death. AIM2 plays a pivotal role in modulating inflammation and tumorigenesis, functioning through both inflammasome-dependent and independent mechanisms. Its influence on the host immune response is dual-faceted, exhibiting both promotive and inhibitory effects in the contexts of inflammation and tumors. These effects are predominantly contingent upon the specific cell type expressing AIM2 and the nature of the host’s disease. This article seeks to review the latest advancements in understanding the cell-specific functions of AIM2 in inflammation and tumorigenesis, with the objective of offering insights for further research on AIM2 and informing the development of targeted therapeutic strategies for clinical application.

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AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity

Cited by 3 publications

References 33 publications

WITHDRAWN: Unveiling the Crucial Role of Pro-inflammatory Macrophages in the Immune Network Imbalance of the maternal-fetal interface with Preeclampsia

WITHDRAWN: Unveiling the Crucial Role of Pro-inflammatory Macrophages in the Immune Network Imbalance of the maternal-fetal interface with Preeclampsia

Impact of AIM2 on HNSCC Development

The role of AIM2 in inflammation and tumors

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