title: Deletion of FoxN1 in the thymic medullary epithelium reduces peripheral T cell responses to infection and mimics changes of aging.
abstract: Aging increases susceptibility to infection, in part because thymic involution culminates in reduced naïve T-lymphocyte output. Thymic epithelial cells (TECs) are critical to ensure normal maturation of thymocytes and production of peripheral T cells. The forkhead-class transcription factor, encoded by FoxN1, regulates development, differentiation, and function of TECs, both in the prenatal and postnatal thymus. We recently showed that expression of FoxN1, by keratin 14 (K14)-expressing epithelial cells is essential for maintenance of thymic medullary architecture, and deletion of FoxN1 in K14 promoter-driven TECs inhibited development of mature TECs and reduced the number of total thymocytes. These findings are reminiscent of changes observed during normal thymic aging. In the current report, we compared the effects of K14-driven FoxN1 deletion on peripheral T cell function in response to influenza virus infection with those associated with normal aging in a mouse model. FoxN1-deleted mice had reduced numbers of peripheral CD62L+CD44- naïve T-cells. In addition, during influenza infection, these animals had reduced antigen-specific CD8+ T-cell and IgG responses to influenza virus, combined with increased lung injury, weight loss and mortality. These findings paralleled those observed in aged wild type mice, providing the first evidence that K14-mediated FoxN1 deletion causes changes in T-cell function that mimic those in aging during an immune response to challenge with an infectious agent.
authors.affiliation: Health Science Center, The University of Texas, Tyler, Texas, United States of America.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Peter
authors.initials: P
authors.lastname: Barnes
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Huang
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Su
authors.forename: Homayoun
authors.initials: H
authors.lastname: Shams
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein