The Innate Lymphoid Cells (ILCs) are a family of innate immune cells composed by the Natural Killer (NK) cells and the helper ILCs (hILCs) (ILC1, ILC2, ILC3), both developing from a common ILC precursor (ILCP) derived from hematopoietic stem cells (HSCs). A correct ILC reconstitution is crucial, particularly in patients receiving HSC transplantation (HSCT), the only therapeutic option for many adult and pediatric high-risk hematological malignancies. Indeed, mainly thanks to their cytotoxic activity, NK cells have a strong Graft-versus-Leukemia (GvL) effect. On the other hand, hILCs, that are mainly tissue resident, are involved in tissue repair and homeostasis, Graft-versus-Host Disease (GvHD) prevention and immune response to infections. Unlike NK cell development, hILC-poiesis is still poorly characterized in humans. Here, we provide a protocol for the in vitro ILC differentiation from healthy donor peripheral blood-derived CD34 HSCs. This could represent a useful model to dissect the molecular mechanisms by which the distinct ILC subsets are generated from ILCP leading to the development of novel strategies to improve the HSCT clinical outcome.
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http://dx.doi.org/10.1016/bs.mcb.2024.10.004 | DOI Listing |
Methods Cell Biol
January 2025
Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
The Innate Lymphoid Cells (ILCs) are a family of innate immune cells composed by the Natural Killer (NK) cells and the helper ILCs (hILCs) (ILC1, ILC2, ILC3), both developing from a common ILC precursor (ILCP) derived from hematopoietic stem cells (HSCs). A correct ILC reconstitution is crucial, particularly in patients receiving HSC transplantation (HSCT), the only therapeutic option for many adult and pediatric high-risk hematological malignancies. Indeed, mainly thanks to their cytotoxic activity, NK cells have a strong Graft-versus-Leukemia (GvL) effect.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear.
View Article and Find Full Text PDFAm J Transplant
December 2024
The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address:
As important immune regulatory cells, whether innate lymphoid cells (ILCs) are involved in liver transplantation (LT) remains unclear. In a murine orthotopic LT model, we dissected roles of ILCs in liver ischemia-reperfusion injury (IRI). Wild-type (WT) grafts suffered significantly higher IRI in Rag2-γc double knockout (DKO) than Rag2 knockout (KO) recipients, in association with downregulation of group 1 ILCs genes, including interferon gamma.
View Article and Find Full Text PDFSTAR Protoc
December 2024
State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Senior Department of Hematology, Fifth Medical Center, Medical Innovation Research Department, Chinese PLA General Hospital, Beijing 100071, China.
Deciphering the origins of innate lymphoid cells (ILCs) is critical for a deeper understanding of innate immunity. Here, we present a protocol for assessing ILC potential of human embryonic resources. We describe steps for identifying lymphoid progenitors in human embryonic tissues, then culturing mature ILCs in vitro, and identifying characteristics and functions of different cultured ILC subsets using cellular indexing of transcriptomes and epitopes (CITE)-sequencing and flow cytometry analysis.
View Article and Find Full Text PDFInvasive lobular carcinoma of the breast (ILC) are typically estrogen receptor α (ER)-positive and present with biomarkers of anti-estrogen sensitive disease, yet patients with ILC face uniquely poor long-term outcomes with increased recurrence risk, suggesting endocrine response and ER function are unique in ILC. We previously found specifically in ILC cells that ER is co-regulated by the DNA repair protein Mediator of DNA Damage Checkpoint 1 (MDC1). This novel MDC1 activity, however, was associated with dysfunction in the canonical DNA repair activity of MDC1, but absent typical features of DNA repair deficiency.
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