T cell Cyp27b1 promotes granzyme B expression and antiviral host defense in a mouse model of H1N1 influenza A virus infection
Year: 2026
Type: article
Abstract: Introduction Immune cells express vitamin D receptors (VDR) and the CYP27B1 enzyme needed to produce the VDR ligand, 1,25(OH) 2 D; suggesting that perhaps the vitamin D response is regulated locally at the site of infection. Here, we examined the role of immune cell-derived 1,25(OH) 2 D in host resistance to influenza infection. Methods Mice were infected with mouse-adapted H1N1 influenza A virus, to determine the role of CYP27B1 on host resistance to influenza infection. The mouse strains infected include; wild type (WT) littermates, whole-body Cyp27b1 knockout (Cyp27b1 KO) mice, mice lacking renal 1,25(OH) 2 D production (double intronic (DI)KO), mice with T cell-specific deletion of Cyp27b1 (T-Cyp27b1 KO), and mice with T cell-specific deletion of Vdr (T-Vdr KO). Results Whole body Cyp27b1 KO mice developed severe influenza A virus disease, including infection induced mortality, compared to WT littermates. Oral treatments of the Cyp27b1 KO mice with 1,25(OH) 2 D failed to completely protect the Cyp27b1 KO mice from influenza A virus disease. Mice without renal 1,25(OH) 2 D had similar influenza disease as WT littermates. Influenza infection of T cell-specific Cyp27b1 KO resulted in increased respiratory distress and lethargy compared to WT littermates. WT and DIKO mice had more CD8+ T cells expressing higher amounts of granzyme B+ (GrzB) and disruptions in PD-1 than either whole-body Cyp27b1 KO or T-Cyp27b1 KO mice. Discussion The work suggests that renal 1,25(OH) 2 D is not required for host resistance to this influenza A virus infection. The work further demonstrates that immune cells and in particular T cells may produce 1,25(OH) 2 D to locally support CD8+ T cell responses to influenza A virus infection. Defining the mechanisms that regulate local 1,25(OH) 2 D production in T cells or other immune cell types is needed.
Source: Frontiers in Immunology
Institution: Pennsylvania State University
Language: English
Topic: Vitamin D Research Studies
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221812486