Inflammatory bowl diseaseHow does vitamin D work?

Vitamin D has several mechanisms whereby it reduces the risk of Crohn's disease (CD).

One is that it regulates the T-helper 1 (Th1) to Th2 balance towards Th2, which generates cytokines that are less proinflammatory including reduced tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in systemic inflammation1.

Another recent paper identified a role for 1,25-dihydroxyvitamin D in affecting expression of the NOD2 gene both directly and indirectly though effects on NF-kB:

Variants in the NOD2/CARD15/IBD1 locus are associated with the strongest risk of development of CD2. NOD2 encodes a protein that is a member of a family of intracellular pattern recognition receptors3. NOD2 recog-nizes modified forms of muramyl didpeptide (MDP), a lysosomal breakdown product of bacterial peptidoglycan. Recent work by one of our team has shown that NOD2 is particularly sensitive to the N-glycolyl form of MDP produced by mycobacteria4

Recently our group found that transcription of the NOD2 gene was stimulated directly by the 1,25D-bound VDR. Regulation of NOD2 expression by 1,25D is noteworthy for several reasons. Signaling through NOD2 induces the function of the NF-kB transcription factor, which in turn induces expression of DEFB2/HBD25 6.

Page last edited: 06 May 2011


  1. Ardizzone, S. Cassinotti, A. Trabattoni, D. Manzionna, G. Rainone, V. Bevilacqua, M. Massari, A. Manes, G. Maconi, G. Clerici, M. Bianchi Porro, G. Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on TH1/TH2 cytokines in inflammatory bowel disease: an in vitro study. Int J Immunopathol Pharmacol. 2009 Jan-Mar; 22 (1): 63-71.
  2. Hugot, J. P. Chamaillard, M. Zouali, H. Lesage, S. Cezard, J. P. Belaiche, J. Almer, S. Tysk, C. O'Morain, C. A. Gassull, M. Binder, V. Finkel, Y. Cortot, A. Modigliani, R. Laurent-Puig, P. Gower-Rousseau, C. Macry, J. Colombel, J. F. Sahbatou, M. Thomas, G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31; 411 (6837): 599-603.
  3. Inohara, N. Ogura, Y. Fontalba, A. Gutierrez, O. Pons, F. Crespo, J. Fukase, K. Inamura, S. Kusumoto, S. Hashimoto, M. Foster, S. J. Moran, A. P. Fernandez-Luna, J. L. Nunez, G. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem. 2003 Feb 21; 278 (8): 5509-12.
  4. Coulombe, F. Divangahi, M. Veyrier, F. de Leseleuc, L. Gleason, J. L. Yang, Y. Kelliher, M. A. Pandey, A. K. Sassetti, C. M. Reed, M. B. Behr, M. A. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med. 2009 Aug 3; 206 (8): 1709-16.
  5. Wang, T. T. Dabbas, B. Laperriere, D. Bitton, A. J. Soualhine, H. Tavera-Mendoza, L. E. Dionne, S. Servant, M. J. Bitton, A. Seidman, E. G. Mader, S. Behr, M. A. White, J. H. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010 Jan 22; 285 (4): 2227-31.
  6. Verway, M. Behr, M. A. White, J. H. Vitamin D, NOD2, autophagy and Crohn's disease. Expert Rev Clin Immunol. 2010 Jul; 6 (4): 505-8.