T cell Cyp27b1 promotes granzyme B expression and antiviral host defense in a mouse model of H1N1 influenza A virus infection
- 1Department of Veterinary and Biomedical Sciences, The Pennsylvania State University
- 2Department of Food and Nutritional Sciences, University of Wisconsin
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.
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BibTeX
@article{froelich2026cell,
title = {{T cell Cyp27b1 promotes granzyme B expression and antiviral host defense in a mouse model of H1N1 influenza A virus infection}},
author = {Nicole E. Froelich and Mengzhu Tang and Nicholas J. Hanna and Troy C. Sutton and Mark B. Meyer and Margherita T. Cantorna},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1944713},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944713/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - T cell Cyp27b1 promotes granzyme B expression and antiviral host defense in a mouse model of H1N1 influenza A virus infection
AU - Nicole E. Froelich
AU - Mengzhu Tang
AU - Nicholas J. Hanna
AU - Troy C. Sutton
AU - Mark B. Meyer
AU - Margherita T. Cantorna
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1944713
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944713/full
AB - 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.
SN - 1664-3224
ER -