Fate-mapping mice: new tools and technology for immune discovery

Lee, Scarlett; Rudd, Brian D.; Smith, Norah L.

doi:10.1016/j.it.2022.01.004

Cited by 9 publications

(5 citation statements)

References 130 publications

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“…Beyond genetic models, photoactivatable or photoconvertible protein labels are also commonly used to address myeloid cell dynamics (Cugurra et al., 2021; Genshaft et al., 2021). Details associated with these approaches are discussed in depth elsewhere (Lee, Rudd, & Smith, 2022). Cre activity is typically regulated downstream of a cell‐specific gene promoter that will restrict LoxP excision to cells of interest.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Fate Mapping

Schrank

Williams

2022

Current Protocols

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Tissue‐resident macrophages are present in all tissues where they perform homeostatic and immune surveillance functions. In many tissues, resident macrophages develop from embryonic progenitors, which mature into a self‐maintaining population through local proliferation. However, tissue‐resident macrophages can be supported by recruited monocyte‐derived macrophages during scenarios such as tissue growth, infection, or sterile inflammation. Circulating blood monocytes arise from hematopoietic stem cell progenitors and possess unique gene profiles that support additional functions within the tissue. Determining cell origins (ontogeny) and cellular turnover within tissues has become important to understanding monocyte and macrophage contributions to tissue homeostasis and disease. Fate mapping, or lineage tracing, is a promising approach to tracking cells based on unique gene expression driving reporter systems, often downstream of a Cre‐recombinase–mediated excision event, to express a fluorescent protein. This approach is typically deployed temporally with developmental stage, disease onset, or in association with key stages of inflammation resolution. Importantly, myeloid fate mapping can be combined with many emerging technologies, including single‐cell RNA‐sequencing and spatial imaging. The application of myeloid cell fate mapping approaches has allowed for impactful discoveries regarding myeloid ontogeny, tissue residency, and monocyte fate within disease models. This protocol outline will discuss a variety of myeloid fate mapping approaches, including constitutive and inducible labeling approaches in adult and embryo tissues. This article outlines basic approaches and models used in mice for fate mapping macrophages. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Adult Fate Mapping Basic Protocol 2: Embryonic Fate Mapping

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Section: Introductionmentioning

confidence: 99%

Macrophage Fate Mapping

Schrank

Williams

2022

Current Protocols

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“…Recent development of fate‐mapping mice allowed to monitor the origin and lifespan of tissue immune cells. [ 48 ] Arg1 CreERT2 and Id2 CreERT2 mice have been used to monitor ILC2 de novo generation by bone‐marrow hematopoiesis and tissue local expansion. Interestingly, in most tested tissues from early adult mice, such as lung, adipose tissue, and intestine, the replenishment of residential ILC2 by de novo generated non‐fate‐mapped ILC2 population remained minimal.…”

Section: Discussionmentioning

confidence: 99%

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

et al. 2023

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Development of abdominal aortic aneurysms (AAA) enhances lesion group‐2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/flIl7rCre/+ mice or induced ILC2 depletion in Icosfl‐DTR‐fl/+Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild‐type (WT) mice, but not ILC2 from Il5−/− mice induces EOS differentiation in bone‐marrow cells from Rorafl/flIl7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5−/− and Il13−/− mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5−/− mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5−/− ILC2 slows AAA growth in Rorafl/flIl7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

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“…An explanation for these findings is that the DN Tr1 cells observed in this study are a heterogeneous population of IL-10-secreting T cells that contains bona fide Tr1 cells that have not yet upregulated either CD49b or LAG-3 and also contains cells that have downregulated these markers as they transition to alternative T cell fates or undergo apoptosis. These questions could be addressed by developing genetic fate-reporting systems for Tr1 cells such as have been described for Th1, Th2, Treg and Th17 cells (Croxford et al, 2009; Lee et al, 2022; Rubtsov et al, 2010). In support of the concept that Tr1 cells exhibit plasticity in vivo , our data indicate that LAG-3 + Tr1 cells in acute IAV infection were capable of transitioning to non-Tr1 cells (loss of IL-10 expression) and also to DP and DN Tr1 cells.…”

Section: Discussionmentioning

confidence: 99%

Novel populations of Tr1 cells contribute to the resolution of acute influenza A virus infection

Abbott

Freimayer

Tyllis

et al. 2022

Preprint

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Type I regulatory (Tr1) cells contribute to immune suppression in the context of chronic infection, autoimmunity, and transplant tolerance. However, their physiological relevance in the resolution of acute respiratory infection is not understood. Here, we identify Tr1 cells accumulating in the lung parenchyma during resolution of the response to sublethal influenza A virus infection in mice. Tr1 cells were dependent on IL-27Ra; and in their absence recovery from IAV-induced weight loss is impaired. Notably, these Tr1 cells did not necessarily co-express the typical Tr1 markers LAG-3 and CD49b, with four distinct populations of Tr1 cells apparent in the lungs. Each population was suppressive and were differentially dependent on IL-10 to mediate suppression. Transcriptional analysis revealed a core Tr1 gene signature in each population and distinct expression profiles indicative of different states of activation and differentiation. Finally, sort-transfer experiments indicated non-linear plasticity between these subsets of Tr1 cells. Together, these data support Tr1 cells contributing to the resolution of acute inflammation and define novel Tr1 cell phenotypes in acute infection.

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Fate-mapping mice: new tools and technology for immune discovery

Cited by 9 publications

References 130 publications

Macrophage Fate Mapping

Macrophage Fate Mapping

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

Novel populations of Tr1 cells contribute to the resolution of acute influenza A virus infection

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