Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis

Mol Immunol. 2008 Nov;46(1):172-80. doi: 10.1016/j.molimm.2008.07.038. Epub 2008 Sep 19.


Probiotics have been shown to exert beneficial effects on modulation of diverse diseases. However, no information is available for the effect of probiotics in the induction of oral tolerance in autoimmune diseases. The main purpose of this study was to elucidate whether Lactobacillus casei (L. casei) affect the induction of oral tolerance in experimental rheumatoid arthritis (RA). Type II collagen (CII) alone or together with L. casei was orally administered into collagen-induced arthritis (CIA) rats, and its effects on the clinical and histopathological aspects of RA were investigated. Co-administration of L. casei with CII more effectively suppressed clinical symptoms, paw swelling, lymphocyte infiltration and destruction of cartilage tissues of experimental arthritis than the rats treated with CII alone. The enhanced therapeutic efficacy was associated with an increase in anti-inflammatory cytokines (IL-10 and TGF-beta) while decreasing pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma and TNF-alpha). Co-administration of L. casei with CII more effectively suppressed CII-reactive T cell proliferation and the levels of Th1-type IgG isotypes (IgG2a and IgG2b), while up-regulating Foxp3 expression levels and the population of Foxp3(+) CD4(+) T cells. Our study provides evidence that L. casei could potentiate antigen-specific oral tolerance and suppress Th1-type immune responses of arthritic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / microbiology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cartilage / drug effects
  • Cartilage / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen Type II / administration & dosage
  • Collagen Type II / pharmacology
  • Down-Regulation / drug effects
  • Female
  • Forkhead Transcription Factors / immunology
  • Immune Tolerance / immunology*
  • Immunoglobulin G / immunology
  • Inflammation / immunology
  • Lacticaseibacillus casei / immunology*
  • Probiotics*
  • Rats
  • Rats, Inbred Lew
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Up-Regulation / drug effects


  • Collagen Type II
  • Forkhead Transcription Factors
  • Foxp3 protein, rat
  • Immunoglobulin G