Biology subjects

Raddi, G.

Publications and source records attributed to Raddi, G..

3 recordsLinked to original sources

bioRxiv2024

Tissue-resident regulatory T cells exert dualistic anti-tumour and pro-repair function in the exocrine pancreas

Regulatory T cells are fundamentally important for maintaining immune homeostasis, and their potent immune-suppressive roles make them attractive immunotherapeutic targets in cancer. Recent work suggests potential functions of tissue-resident Tregs (trTregs) in tissue-repair and epithelial cell homeostasis. Here, we describe a rare population of trTreg in the exocrine pancreas. We show that these cells share common features of trTregs, including expression of the IL-33 receptor ST2 and production of the epithelial growth factor Amphiregulin, and display an oligoclonal T cell receptor repertoire. Using a mouse model of acute pancreatitis, we show that pancreatic Tregs rapidly expand upon release of IL-33 by fibroblasts. Moreover, depletion of Tregs after initiation of pancreatic injury impairs the regeneration of the exocrine parenchyma. This effect is due, in part, through a direct effect of Tregs on acinar cell proliferation. Finally, we show that transient Treg depletion in established orthotopic pancreatic tumours leads to tumour rejection yet provokes long-lasting damages to surrounding exocrine parenchyma. In all, our results demonstrate the tissue-repair capacity of pancreatic Tregs, and highlight a dualistic role of these cells in the pancreatic tumour ecosystem, with their harmful immune-suppressive function in the tumour coupled to a beneficial tissue-repair function in the surrounding tissue.

immunology↗

bioRxiv2021

Toll signaling enhances mosquito antiplasmodial immunity by promoting differentiation of hemocytes to the Megacyte lineage

Silencing Cactus, a suppressor of Toll signaling, in Anopheles gambiae, eliminates Plasmodium ookinetes by enhancing local release of hemocyte-derived microvesicles that promote activation of the mosquito complement-like system. We report that Cactus silencing dramatically increases the proportion of megacytes, a new effector hemocyte subpopulation of large granulocytes, from 5 to 79% of circulating granulocytes. Transcriptomic and morphological analysis, as well as cell counts, in situ hybridization and expression of cell-specific markers, indicate that Cactus silencing triggers granulocyte differentiation into megacytes, a process mediated by the Rel1 transcription factor of the Toll pathway. Megacytes are very plastic cells that can extend long filopodia, tend to form clusters in vivo, and are massively recruited to the basal midgut surface in response to bacterial feeding and Plasmodium infection. We show that hemocyte differentiation to the megacyte lineage greatly enhances mosquito immunity against Plasmodium.

microbiology↗

bioRxiv2020

Mosquito cellular immunity at single-cell resolution

Insect hemocytes are the functional equivalents of leukocytes and limit the capacity of mosquitoes to transmit human pathogens through phagocytosis, encapsulation, secretion of immune factors and immune priming (1, 2). Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti, two important mosquito vectors. Blood feeding, infection with malaria parasites and other immune challenges reveal a previously unknown functional diversity of hemocytes, with different types of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A new cell type, which we term megacyte, is defined in Anopheles by a unique transmembrane protein marker (TM7318) and high expression of LPS-Induced TNF-alpha transcription factor 3 (LL3). Knock-down experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify two main hemocyte lineages and find evidence of proliferating granulocyte populations. We validate our analysis with RNA in-situ hybridization and highlight the mobilization of sessile hemocytes into circulation upon infection. Our data (https://hemocytes.cellgeni.sanger.ac.uk/) provide the first atlas of medically relevant invertebrate immune cells at single cell resolution. It provides an important resource for invertebrate immunology by identifying cellular events that underpin mosquito immunity to malaria infection.

immunology↗