CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Monica MacalElina I Zuniga

Abstract

Type I IFNs (IFN-I) are key innate mediators that create a profound antiviral state and orchestrate the activation of almost all immune cells. Plasmacytoid dendritic cells (pDCs) are the most powerful IFN-I-producing cells and play important roles during viral infections, cancer, and autoimmune diseases. By comparing gene expression profiles of murine pDCs and conventional DCs, we found that CD28, a prototypic T cell stimulatory receptor, was highly expressed in pDCs. Strikingly, CD28 acted as a negative regulator of pDC IFN-I production upon TLR stimulation but did not affect pDC survival or maturation. Importantly, cell-intrinsic CD28 expression restrained pDC (and systemic) IFN-I production during in vivo RNA and DNA viral infections, limiting antiviral responses and enhancing viral growth early after exposure. Finally, CD28 also downregulated IFN-I response upon skin injury. Our study identified a new pDC regulatory mechanism by which the same CD28 molecule that promotes stimulation in most cells that express it is co-opted to negatively regulate pDC IFN-I production and limit innate responses.

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Citations

Nov 5, 2016·The Journal of Experimental Medicine·Romain RoncagalliBernard Malissen
Jan 11, 2019·International Journal of Molecular Sciences·Austin K MircheffChuanqing Ding
Nov 25, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica L Turnier, J Michelle Kahlenberg
Nov 11, 2020·European Journal of Immunology·Lizbeth Estrada-CapetilloAmaya Puig-Kröger
Oct 31, 2020·Cell·Lydia KalafatiTriantafyllos Chavakis
May 1, 2021·International Journal of Molecular Sciences·Dóra BenczeKitti Pázmándi

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