Transcriptional modulation of pattern recognition receptors in chronic colitis in mice is accompanied with Th1 and

Bin Zheng1, Mary E Morgan1, Hendrik J G van de Kant1

  • 1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht 3586 CG, The Netherlands.

Insights

Pattern recognition receptors (PRRs) expression changes in chronic colitis models reveal a persistent Th1 and Th17 immune response. This study highlights specific PRR alterations during chronic inflammation in the gut.

Area of Science:

  • Immunology
  • Gastroenterology

Background:

  • Pattern recognition receptors (PRRs) sense microbes and may influence inflammatory bowel diseases (IBD).
  • The gut microenvironment in IBD is unique and can impact PRR function.

Purpose of the Study:

  • To investigate the mRNA expression profile of PRRs in the colon during chronic colitis.
  • To examine T cell-associated factors and Foxp3+ cell infiltration in a chronic colitis mouse model.

Main Methods:

  • A chronic colitis mouse model was established using repeated dextran sodium sulfate (DSS) treatments.
  • Colonic mRNA expression of PRRs and T cell factors was measured.
  • Histological analysis and Foxp3+ cell scoring were performed.

Main Results:

  • Chronic colitis showed histological inflammation, but not clinical symptoms.
  • Nod1 decreased while Nod2 increased; Tlr3 and Tlr4 were enhanced after the third DSS treatment.
  • Tlr5 mRNA decreased and Tlr9 increased persistently during chronic colitis.
  • Ifnγ and Il17 mRNA remained elevated, while Il23, Il10, and Il12 increases were abolished.
  • Foxp3+ cell infiltration in the colon was increased.

Conclusions:

  • Chronic colitis is characterized by specific PRR expression patterns, including persistent decreases in Tlr5 and increases in Tlr9.
  • The immune response in chronic colitis involves elevated Ifnγ and Il17, indicating a Th1 and Th17 cell-mediated response.
  • Increased Foxp3+ cells suggest a role for regulatory T cells in chronic gut inflammation.

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