Contributions of Nonhematopoietic Cells and Mediators to Immune Responses: Implications For Immunotoxicology

ORCID

Kaplan: 0000-0002-1992-4145

MSU Affiliation

College of Veterinary Medicine; Department of Basic Sciences; Center for Environmental Health Sciences

Creation Date

2026-03-02

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.

Publication Date

6-1-2015

Publication Title

Toxicological Sciences

Publisher

Oxford University Press

First Page

214

Last Page

232

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Digital Object Identifier (DOI)

https://doi.org/10.1093/toxsci/kfv060