tetano
Editor, Senior Moderator
Front Immunol
. 2026 Oct 14:17:1944713.
doi: 10.3389/fimmu.2026.1944713. eCollection 2026.
Nicole E Froelich 1 , Mengzhu Tang 1 , Nicholas J Hanna 1 , Troy C Sutton 1 , Mark B Meyer 2 , Margherita T Cantorna 1
Affiliations Expand
Introduction: Immune cells express vitamin D receptors (VDR) and the CYP27B1 enzyme needed to produce the VDR ligand, 1,25(OH)2D; 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)2D 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)2D 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)2D failed to completely protect the Cyp27b1 KO mice from influenza A virus disease. Mice without renal 1,25(OH)2D 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)2D 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)2D to locally support CD8+ T cell responses to influenza A virus infection. Defining the mechanisms that regulate local 1,25(OH)2D production in T cells or other immune cell types is needed.
Keywords: CD8+ T cells; Cyp27b1 1α-hydroxylase; granzyme B; influenza A virus; vitamin D.
. 2026 Oct 14:17:1944713.
doi: 10.3389/fimmu.2026.1944713. eCollection 2026.
T cell Cyp27b1 promotes granzyme B expression and antiviral host defense in a mouse model of H1N1 influenza A virus infection
Nicole E Froelich 1 , Mengzhu Tang 1 , Nicholas J Hanna 1 , Troy C Sutton 1 , Mark B Meyer 2 , Margherita T Cantorna 1
Affiliations Expand
- PMID: 42952597
- PMCID: PMC13713429
- DOI: 10.3389/fimmu.2026.1944713
Abstract
Introduction: Immune cells express vitamin D receptors (VDR) and the CYP27B1 enzyme needed to produce the VDR ligand, 1,25(OH)2D; 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)2D 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)2D 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)2D failed to completely protect the Cyp27b1 KO mice from influenza A virus disease. Mice without renal 1,25(OH)2D 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)2D 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)2D to locally support CD8+ T cell responses to influenza A virus infection. Defining the mechanisms that regulate local 1,25(OH)2D production in T cells or other immune cell types is needed.
Keywords: CD8+ T cells; Cyp27b1 1α-hydroxylase; granzyme B; influenza A virus; vitamin D.