title: In situ hematopoiesis: a regulator of TH2 cytokine-mediated immunity and inflammation at mucosal surfaces.
abstract: Hematopoiesis refers to the development of blood cells in the body through the differentiation of pluripotent stem cells. Although hematopoiesis is a multifocal process during embryonic development, under homeostatic conditions it occurs exclusively within the bone marrow. There, a limited number of hematopoietic stem cells differentiate into a rapidly proliferating population of lineage-restricted progenitors that serve to replenish circulating blood cells. However, emerging reports now suggest that under inflammatory conditions, alterations in hematopoiesis that occur outside of the bone marrow appear to constitute a conserved mechanism of innate immunity. Moreover, recent reports have identified previously unappreciated pathways that regulate the egress of hematopoietic progenitor cells from the bone marrow, alter their activation status, and skew their developmental potential. These studies suggest that progenitor cells contribute to inflammatory response by undergoing in situ hematopoiesis (ISH). In this review, we highlight the differences between homeostatic hematopoiesis, which occurs in the bone marrow, and ISH, which occurs at mucosal surfaces. Further, we highlight factors produced at local sites of inflammation that regulate hematopoietic progenitor cell responses and the development of TH2 cytokine-mediated inflammation. Finally, we discuss the therapeutic potential of targeting ISH in preventing the development of inflammation at mucosal sites.
authors.affiliation: Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C C K
authors.initials: CC
authors.lastname: Hui
authors.affiliation: Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: K M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Denburg
authors.affiliation: Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Siracusa
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006376:Helminths / Q000276:immunology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007109:Immunity; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins