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Cutting Edge: Peyer’s Patch Plasmacytoid Dendritic Cells (pDCs) Produce Low Levels of Type I Interferons: Possible Role for IL-10, TGF, and Prostaglandin E₂ in Conditioning a Unique Mucosal pDC Phenotype¹

Nikhat Contractor^*,, Jennifer Louten^,, Leesun Kim^*, Christine A. Biron and Brian L. Kelsall^2,*

^* Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; Wyeth Nutrition, Collegeville, PA 19426; and Schering-Plough Biopharma, Palo Alto, CA 94304

The organized lymphoid tissues of the intestine likely play an important role in the balance between tolerance harmless mucosal Ags and commensal bacteria and immunity to mucosal pathogens. We examined the phenotype and function of plasmacytoid dendritic cells (pDCs) from murine Peyer’s patches (PPs). When stimulated with CpG-enriched oligodeoxynucleotides in vitro, PPs and spleen pDCs made equivalent levels of IL-12, yet PP pDCs were incapable of producing significant levels of type I IFNs. Three regulatory factors associated with mucosal tissues, PGE₂, IL-10, and TGF, inhibited the ability of spleen pDCs to produce type I IFN in a dose-dependent fashion. These studies suggest that mucosal factors may regulate the production of type I IFN as well as IL-12 by pDCs. In the intestine, this may be beneficial in preventing harmful innate and adaptive immune responses to commensal microorganisms.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the Intramaral Research Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH). In addition, C.B. and J.L. were supported by NIH Grant number RO1 AI 55677.

² Address correspondence and reprint requests to Dr. Brian Kelsall, 10/11N111, 10 Center Drive, Bethesda, MD 20892. E-mail address: kelsall{at}nih.gov

³ Abbreviations used in this paper: PP, Peyer’s patch; cDC, conventional dendritic cell; FLT3L, FMS-like tyrosine kinase 3 ligand; int, intermediate; LP, lamina propria; mPDCA, murine pDC Ag; ODN, oligodeoxynucleotide; pDC, plasmacytoid dendritic cell.