title: Contributions of nonhematopoietic cells and mediators to immune responses: implications for immunotoxicology.
abstract: Immunotoxicology assessments have historically focused on the effects that xenobiotics exhibit directly on immune cells. These studies are invaluable as they identify immune cell targets and help characterize mechanisms and/or adverse outcome pathways of xenobiotics within the immune system. However, leukocytes can receive environmental cues by cell-cell contact or via released mediators from cells of organs outside of the immune system. These organs include, but are not limited to, the mucosal areas such as the lung and the gut, the liver, and the central nervous system. Homeostatic perturbation in these organs induced directly by toxicants can initiate and alter the outcome of local and systemic immunity. This review will highlight some of the identified nonimmune influences on immune homeostasis and provide summaries of how immunotoxic mechanisms of selected xenobiotics involve nonimmune cells or mediators. Thus, this review will identify data gaps and provide possible alternative mechanisms by which xenobiotics alter immune function that could be considered during immunotoxicology safety assessment.
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi St, Mississippi 39762, Safety Assessment, Genentech, Inc. South San Francisco, California 94080, Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Barbara L F
authors.initials: BL
authors.lastname: Kaplan
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi St, Mississippi 39762, Safety Assessment, Genentech, Inc. South San Francisco, California 94080, Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Jinze
authors.initials: J
authors.lastname: Li
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi St, Mississippi 39762, Safety Assessment, Genentech, Inc. South San Francisco, California 94080, Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: John J
authors.initials: JJ
authors.lastname: LaPres
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi St, Mississippi 39762, Safety Assessment, Genentech, Inc. South San Francisco, California 94080, Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Pruett
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi St, Mississippi 39762, Safety Assessment, Genentech, Inc. South San Francisco, California 94080, Department of Biochemistry and Molecular Biology, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105 peer.karmaus@stjude.org.
authors.forename: Peer W F
authors.initials: PW
authors.lastname: Karmaus
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014116:Toxicology / Q000379:methods*; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D015262:Xenobiotics
keywords: immunotoxicology; nonhematopoietic cells; xenobiotics