Publication Date

2015

Journal Title

Immunol Res

Abstract

The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, and extracellular vesicles play a crucial role in initiating an innate immune response. IL-36gamma is a pro-inflammatory member of the IL-1 family that is mainly expressed by epithelial cells, but regulation of its expression and release are only beginning to be understood. Previous studies reported that IL-36gamma is abundant in recurrent respiratory papillomatosis, a rare but devastating disease caused by human papillomaviruses (HPV) types 6 and 11, in which papillomas recurrently grow in and block the airway. Despite the overexpression of IL-36gamma, papilloma tissues show no evidence of inflammation, possibly due to suppression of its release by HPVs. We have used primary human foreskin keratinocytes as a model to study IL-36gamma regulation in normal epithelial cells. Low doses of poly(I:C) mediate expression and release of IL-36gamma without inducing the cell death reported by those using high doses. PKR, an enzyme required for inflammasome activation, does not contribute to controlled release of IL36gamma. The keratinocytes secrete IL-36gamma in two forms, soluble and in extracellular vesicles. We conclude that there are two separately regulated pathways for the controlled secretion of IL-36gamma from keratinocytes, which could contribute to the modulation of both local and systemic immune responses to viruses and other pathogens.

Volume Number

63

Issue Number

1-3

Pages

228-35

Document Type

Article

EPub Date

2015/09/27

Status

Faculty; Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Pediatrics; Medicine; Otolaryngology

PMID

26407986

DOI

10.1007/s12026-015-8692-7


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