Invariant NKT cell defects in vitamin D receptor knockout mice prevents experimental lung inflammation

Sanhong Yu, Jun Zhao, Margherita T. Cantorna

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Vitamin D receptor (VDR) deficiency (knockout [KO]) results in a failure of mice to generate an airway hyperreactivity (AHR) response on both the BALB/c and C57BL/6 background. The cause of the failed AHR response is the defective population of invariant NKT (iNKT) cells in the VDR KO mice because wild-type (WT) iNKT cells rescued the AHR response. VDR KO mice had significantly fewer iNKT cells and normal numbers of T cells in the spleen compared with WT mice. In BALB/c VDR KO mice, the reduced frequencies of iNKT cells were not apparent in the liver or thymus. VDR KO and WT Th2 cells produced similar levels of IFN-γ and IL-5. On the BALB/c background, Th2 cells from VDR KO mice produced less IL-13, whereas on the C57BL/6 background, Th2 cells from VDR KO mice produced less IL-4. Conversely, VDR KO iNKT cells were defective for the production of multiple cytokines (BALB/c: IL-4, IL-5, and IL-13; C57BL/6: IL-4 and IL-17). Despite relatively normal Th2 responses, BALB/c and C57BL/6 VDR KO mice failed to develop AHR responses. The defect in iNKT cells as a result of the VDR KO was more important than the highly susceptible Th2 background of the BALB/c mice. Defective iNKT cell responses in the absence of the VDR result in the failure to generate AHR responses in the lung. The implication of these mechanistic findings for human asthma requires further investigation.

Original languageEnglish (US)
Pages (from-to)4907-4912
Number of pages6
JournalJournal of Immunology
Volume187
Issue number9
DOIs
StatePublished - Nov 1 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Invariant NKT cell defects in vitamin D receptor knockout mice prevents experimental lung inflammation'. Together they form a unique fingerprint.

Cite this