Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells

Lukowski, Samuel W.; Rødahl, Inga; Kelly, S. Thomas; Yu, Meihua; Gotley, James; Zhou, Chenhao; Millard, Susan; Andersen, Stacey; Christ, Angelika N.; Belz, Gabrielle T.; Frazer, Ian H.; Chandra, Janin

doi:10.1016/j.isci.2021.102402

Cited by 19 publications

(20 citation statements)

References 51 publications

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“…Several scRNA-seq studies supported similar populations as cDC precursors ( 44 , 46 , 63 ). Similarly, Lukowski et al ( 64 ) identified a cluster of Sox4 + cDCs in the murine spleen, displaying a continuum of cDC and pDC lineage-mixed gene signatures, which had a similar transcriptional profile with AS DCs in humans. This population expressed elevated levels of pre-DC features (such as CX3CR1, FLT3, CD33, and CSF1R) and was hypothesized to represent a cell state of pre-DC to cDC transition.…”

Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 89%

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

et al. 2021

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Dendritic cells (DCs) play essential roles in innate and adaptive immunity and show high heterogeneity and intricate ontogeny. Advances in high-throughput sequencing technologies, particularly single-cell RNA sequencing (scRNA-seq), have improved the understanding of DC subsets. In this review, we discuss in detail the remarkable perspectives in DC reclassification and ontogeny as revealed by scRNA-seq. Moreover, the heterogeneity and multifunction of DCs during diseases as determined by scRNA-seq are described. Finally, we provide insights into the challenges and future trends in scRNA-seq technologies and DC research.

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Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 89%

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

et al. 2021

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“…These data suggest there may be two possible cross presentation pathways for IEC-derived antigen: one that occurs in the presence, and one in the absence, of inflammatory signals. Indeed, recent work shows that cDC2s can take on characteristics of cDC1s under inflammatory conditions (Bosteels et al, 2020) or in the absence of Batf3 (Lukowski et al, 2021), though it remains uncertain if these cells are able to cross prime CD8 + T cells or provide T cells with the appropriate homing signals. Perhaps IL-18 and/or other inflammatory signals downstream of NAIP–NLRC4 activation can activate cDC1-like capabilities of cDC2s in our OvaFla system.…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-dependent and -independent cross-priming of CD8⁺ T cells by intestinal epithelial cell-derived antigen

Rauch

et al. 2021

Preprint

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The innate immune system detects pathogens and initiates adaptive immune responses. Inflammasomes are central components of the innate immune system, but whether inflammasomes provide sufficient signals to activate adaptive immunity is unclear. In intestinal epithelial cells (IECs), inflammasomes activate a lytic form of cell death called pyroptosis, leading to epithelial cell expulsion and the release of cytokines. Here we employed a genetic system to show that simultaneous antigen expression and inflammasome activation specifically in IECs is sufficient to activate CD8+ T cells. By genetic elimination of direct T cell priming by IECs, we found that IEC-derived antigens are cross-presented to CD8+ T cells. However, activation of CD8+ T cells by IEC-derived antigen only partially depended on IEC pyroptosis. In the absence of inflammasome activation, cross-priming of CD8+ T cells required Batf3+ dendritic cells (cDC1), whereas cross-priming in the presence of pyroptosis did not. These data suggest the existence of parallel pyroptosis-dependent and pyroptosis-independent but cDC1-dependent pathways for cross-presentation of IEC-derived antigens.

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“…cDC1s present exogenous Ags and secretes IL-12, leading to a cell-based immune response. They present Ags on MHCII to stimulate the activation of CD4 + T helper type 1 cells (Th1), and they are specialized in the cross-presentation of exogenous Ags on MHCI to stimulate the activation CD8 + T cells (cytotoxic killer cells) [ 79 , 80 ].…”

Section: DC Subsets and Their Immunological Rolesmentioning

confidence: 99%

Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

Brandum

Jørgensen

Hjortø

2021

IJMS

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Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC–T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.

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Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells

Abstract: Single-cell proteogenomics identifies additional layers of DC heterogeneity cDC diversity is driven by proliferation, developmental stage, and maturation Lack of Batf3 increases cDCs with lineage-mixed features Sox4+ cDCs represent a cell state of lineage-mixed features

Cited by 19 publications

References 51 publications

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

Pyroptosis-dependent and -independent cross-priming of CD8⁺ T cells by intestinal epithelial cell-derived antigen

Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

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Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells

Abstract: Single-cell proteogenomics identifies additional layers of DC heterogeneity cDC diversity is driven by proliferation, developmental stage, and maturation Lack of Batf3 increases cDCs with lineage-mixed features Sox4+ cDCs represent a cell state of lineage-mixed features

Cited by 19 publications

References 51 publications

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

Pyroptosis-dependent and -independent cross-priming of CD8+ T cells by intestinal epithelial cell-derived antigen

Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

Contact Info

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Resources

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Pyroptosis-dependent and -independent cross-priming of CD8⁺ T cells by intestinal epithelial cell-derived antigen