Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients

Enzo Candia, David Díaz-Jiménez, Patricia Langjahr, Lucía E. Núñez, Marjorie de la Fuente, Nancy Farfán, Francisco López-Kostner, Mario Abedrapo, Manuel Alvarez-Lobos, George Pinedo, Caroll J. Beltrán, Carlos González, María Julieta González, Rodrigo Quera, Marcela A. Hermoso

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Toll-like receptor 2 (TLR2) is a type I pattern recognition receptor that has been shown to participate in intestinal homeostasis. Its increased expression in the lamina propria has been associated with the pathogenesis in inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). Recently, soluble TLR2 (sTLR2) variants have been shown to counteract inflammatory responses driven by the cognate receptor. Despite the evident roles of TLR2 in intestinal immunity, no study has elucidated the production and cellular source of sTLR2 in IBD. Furthermore, an increase in the population of activated macrophages expressing TLR2 that infiltrates the intestine in IBD has been reported. We aimed first to assess the production of the sTLR2 by UC and CD organ culture biopsies and lamina propria mononuclear cells (LPMCs) as well as the levels of sTLR2 in serum, and then characterize the cell population from lamina propria producing the soluble protein.Mucosa explants, LPMCs and serum were obtained from UC, CD patients and control subjects. The level of sTLR2 was higher in conditioned media from organ culture biopsies and LPMCs from UC patients in comparison to CD and controls. Moreover, an inverse correlation between the content of intestinal and serum sTLR2 levels was observed in UC patients. Additionally, when characterizing the cellular source of the increased sTLR2 by LPMCs from UC patients, an increase in TLR2+/CD33+ cell population was found. Also, these cells expressed CX3CR1, which was related to the increased levels of intestinal FKN in UC patients, suggesting that a higher proportion of TLR2+ mononuclear cells infiltrate the lamina propria. The increased production of sTLR2 suggests that a differential regulating factor of the innate immune system is present in the intestinal mucosa of UC patients.

Original languageEnglish
Pages (from-to)634-642
Number of pages9
JournalImmunobiology
Volume217
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by the Science and Technology Foundation of Chile (FONDECYT) grant 1080290 and by the Academic Direction of Las Condes Clinic (DA-CLC) grant PI200909 . The authors wish to thank all patients and control subjects for their participation in this study. Finally, we want to thank A. Calixto and A. Ferreira for critically revising the manuscript and to C. Muñoz and I. Contreras for their constructive support in the immuno-histochemistry studies.

Keywords

  • Inflammatory bowel diseases
  • Monocytes
  • Toll-like receptor 2
  • Ulcerative colitis

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