The emerging family of RORγt+ antigen-presenting cells

Abramson, Jakub; Dobeš, Jan; Lyu, Mengze; Sonnenberg, Gregory F.

doi:10.1038/s41577-023-00906-5

Cited by 21 publications

(10 citation statements)

References 107 publications

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“…Finally, it has recently been suggested by Abramson et al that TC IV i) may not express the RORγt isoform and ii) that their existence has not been independently confirmed by other studies 7 . However, we now show that Itgb8-expressing TC IV cells were captured and profiled in the scRNA-seq analysis by Lyu et al, in which cells were sorted on the basis of GFP expression driven by the RORγt promoter.…”

mentioning

confidence: 91%

Reconciling the spectrum of RORγt⁺antigen-presenting cells

Park,

Leslie,

Rudensky

et al. 2023

Preprint

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Three recent contemporaneously published papers1–3showed that antigen-presenting cells (APC) expressing the nuclear receptor RORγt instruct peripheral regulatory T (pTreg) cell differentiation and establish tolerance to the gut microbiota. These studies identified a spectrum of RORγt+APCs, distinct from dendritic cells, that included type 3 innate lymphoid cells (ILC3s) as well as novel APC types. Given the discordant conclusions as to the nature of the pTreg-inducing APC and the divergent nomenclature used in these three studies, there is a clear need to reconcile these analyses and the identity of the cell types described. Our reanalysis of the single cell RNA-seq data from these studies revealed the presence of four distinct subsets of non-ILC3 RORγt+APCs, present in all three datasets reported, and confirmed expression of Itgb8, the critical factor for RORγt+APC mediated pTreg induction, in cells synonymous with the non-Aire expressing Thetis cell subset, TC IV.

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mentioning

confidence: 91%

Reconciling the spectrum of RORγt⁺antigen-presenting cells

Park,

Leslie,

Rudensky

et al. 2023

Preprint

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“…Antigen-Presenting Cells (APCs), key components of the immune system, are primarily responsible for capturing, processing, and presenting antigens to T cells, thereby activating and regulating adaptive immune responses. , Macrophages and dendritic cells (DCs) are two important types of APCs. Based on our previous findings, we observed that BMCV treatment disrupted the intact structure of S.…”

Section: Resultsmentioning

confidence: 99%

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression

Jiang,

Wang,

Ren

et al. 2024

ACS Nano

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The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO 2 @Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H 2 O 2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigenpresenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

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“…RoRγt is critical for the development of ILC3, which have been implicated as drivers of innate models of IBD [5,33]. Despite this, RoRγt is largely dispensable for innate colitis in TRAG mice.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the development of ILC3, RoRγt regulates the expression of IL23R and thus responsiveness of intestinal ILC3 to IL23 [33]. In the anti-CD40 antibody and H. hepaticus induced models of innate colitis, RoRγt-dependent ILC3 are required for development of colitis [5].…”

Section: Discussionmentioning

confidence: 99%

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

Torres-Huerta,

Ruley-Haase,

Reed

et al. 2024

PLoS ONE

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Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

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The emerging family of RORγt+ antigen-presenting cells

Cited by 21 publications

References 107 publications

Reconciling the spectrum of RORγt⁺antigen-presenting cells

Reconciling the spectrum of RORγt⁺antigen-presenting cells

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

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The emerging family of RORγt+ antigen-presenting cells

Cited by 21 publications

References 107 publications

Reconciling the spectrum of RORγt+antigen-presenting cells

Reconciling the spectrum of RORγt+antigen-presenting cells

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

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Reconciling the spectrum of RORγt⁺antigen-presenting cells

Reconciling the spectrum of RORγt⁺antigen-presenting cells