B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing

Frede, Annika; Czarnewski, Paulo; Monasterio, Gustavo; Tripathi, Kumar Parijat; Bejarano, David Alejandro; Flores, Ricardo O. Ramirez; Sorini, Chiara; Larsson, Ludvig; Luo, Xinxin; Geerlings, Laura; Novella-Rausell, Claudio; Zagami, Chiara; Kuiper, Raoul V.; Morales, Rodrigo A.; Castillo, Francisca; Hunt, Matt; Mariano, Lívia Lacerda; Hu, Yue; Engblom, Camilla; Lennon-Duménil, Ana-María; Mittenzwei, Romy; Westendorf, Astrid M.; Hövelmeyer, Nadine; Lundeberg, Joakim; Sáez-Rodríguez, Julio; Schlitzer, Andreas; Das, Srustidhar; Villablanca, Eduardo J.

doi:10.1016/j.immuni.2022.11.002

Cited by 48 publications

(31 citation statements)

References 88 publications

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“…We found EI macrophages that were entirely surrounded by Ter119 + erythroblasts, as expected, but frequently observed cell-cell interactions of macrophages with c-Kit + progenitors and CD150 + LT-HSCs (Figure 3A). To determine whether LT-HSCs interact with distinct macrophage populations, we assessed cellular interactions via co-detection by indexing (CODEX)-enabled high-dimensional imaging (Black et al, 2021; Frede et al, 2022; Goltsev et al, 2018), validating the presence of clusters A-D identified by flow cytometry. CD45, Iba1, F4/80, Cx3cr1 and Tim4 were used as pan-macrophage markers (Figure 3B), allowing the distinction of cluster A: CD106 (Vcam1) + macrophages, cluster B: CD206 + macrophages, cluster C: CD169 + macrophages and the most abundant cluster D: Ter119 + EI macrophages (Figure 3B, Figure S3A).…”

Section: Resultsmentioning

confidence: 99%

Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis

Kayvanjoo

Šplíchalová

Bejarano

et al. 2023

Preprint

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During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.

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Section: Resultsmentioning

confidence: 99%

Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis

Kayvanjoo

Šplíchalová

Bejarano

et al. 2023

Preprint

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“…Further evidence of the importance of these signals was recently shown in experiments using an antibody that engages FZD receptors, working as a WNT analogue, which restored barrier integrity after dextran sulphate sodium‐induced colitis (Xie et al., 2022). Additionally, the importance of epithelial–stroma communication in colonic regeneration after chemical injury in mice is further supported by evidence showing that a B cell‐mediated disruption of this network delays recovery from dextran sulphate sodium‐induced colitis (Frede et al., 2022). In addition to fibroblast‐mediated epithelial regulation, there is also evidence of fibroblast activation in response to epithelial cell damage.…”

Section: Introductionmentioning

confidence: 92%

Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators

Miki

Manresa

2023

The Journal of Physiology

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Fibroblasts are essential components of the stroma, sustaining a variety of tissues and being key to the process of tissue repair after injury. Their role in tissue repair has been attributed to their ability to acquire a contractile, extracellular matrix‐producing phenotype known as myofibroblasts. This property is primarily dependent on their response to the pleiotropic cytokine transforming growth factor‐β1. Until recently, the potential role of fibroblasts in other homeostatic and disease‐related processes was less well understood. Although in vitro studies indicated that fibroblasts are able to respond to and secrete inflammatory mediators, definitive evidence of their contribution to chronic inflammation was limited. However, the emergence of techniques that allow exploration of tissues at the single cell level has challenged the previous paradigms on fibroblast identity and functions, and has led to the discovery of significant diversity, showing the presence of fibroblasts with alternate transcriptional profiles in a variety of tissues. These studies have also suggested potential roles of novel fibroblast subtypes as regulators of epithelial homeostasis and renewal, inflammatory cell infiltration and activation, and antigen presentation. Here, we provide a comprehensive review of the recent literature on fibroblast diversity in the digestive tract, skin, lungs and joints. We also review evidence of their contribution to the regulation of homeostasis and chronic inflammation, as well as their interactions with other cells in various tissue compartments. We discuss evidence of different factors involved in the control of fibroblast function, addressing the role of various cytokines, transcription factors and epigenetic changes, as well as microenvironmental factors, including extracellular matrix stiffness, hypoxia, and metabolic shifts.

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“…While lymphoid organoids have been successfully generated in vitro [ 108 , 109 ], the recapitulation or study of B cells in tumour organoids remains challenging and hence very limited [ 45 ]. As more research has uncovered the multifarious roles of B cells in the TME [ 110 ], further work on B-cell-containing tumour organoids may be necessary.…”

Section: Translational Immuno-oncology Research With Organoidsmentioning

confidence: 99%

Organoids as an Enabler of Precision Immuno-Oncology

Zhao

Fong

Seow

et al. 2023

Cells

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Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies. The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion. As the complexity of TME has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types. Here, we discuss how organoids can study the TME across cancers and how these features may improve precision I/O. We outline the approaches to preserve or recapitulate the TME in tumour organoids and discuss their potential, advantages, and limitations. We will discuss future directions of organoid research in understanding cancer immunology in-depth and identifying novel I/O targets and treatment strategies.

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B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing

Cited by 48 publications

References 88 publications

Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis

Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis

Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators

Organoids as an Enabler of Precision Immuno-Oncology

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