Inhibiting retinoic acid signaling in dendritic cells suppresses respiratory syncytial virus infection through enhanced antiviral immunity.

Autor:	Farazuddin M; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Acker G; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Zourob J; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., O'Konek JJ; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Wong PT; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Morris S; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Rasky AJ; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Kim CH; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Lukacs NW; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Baker JR Jr; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 May 24; Vol. 27 (7), pp. 110103. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110103
Abstrakt:	Retinoic acid (RA), controls the immunoregulatory functions of many immune cells, including dendritic cells (DCs), and is important for mucosal immunity. In DCs, RA regulates the expression of pattern recognition receptors and stimulates interferon production. Here, we investigated the role of RA in DCs in mounting immunity to respiratory syncytial virus (RSV). To abolish RA signaling in DCs, we used mice expressing a dominant negative form of retinoic acid receptor-α (RARα) under the CD11c promoter (CD11c-dnRARα). Paradoxically, upon RSV challenge, these animals had lower viral burden, reduced pathology, and greater Th1 polarized immunity than wild-type (WT) mice. Moreover, CD11c-dnRARα DCs infected with RSV showed enhancement in innate and adaptive immunity genes, while genes associated with viral replication were downregulated. These findings suggest that the absence of RA signaling in DCs enhances innate immunity against RSV infection leading to decreased viral load and reduced pathogenicity. Competing Interests: The authors declare no competing interests. (© 2024 The Authors.)
Databáze:	MEDLINE
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