title: Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients.
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.
authors.affiliation: Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, CL 8380453, Chile.
authors.forename: Enzo
authors.initials: E
authors.lastname: Candia
authors.forename: David
authors.initials: D
authors.lastname: Díaz-Jiménez
authors.forename: Patricia
authors.initials: P
authors.lastname: Langjahr
authors.forename: Lucía E
authors.initials: LE
authors.lastname: Núñez
authors.forename: Marjorie
authors.initials: M
authors.lastname: de la Fuente
authors.forename: Nancy
authors.initials: N
authors.lastname: Farfán
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Kostner
authors.forename: Mario
authors.initials: M
authors.lastname: Abedrapo
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez-Lobos
authors.forename: George
authors.initials: G
authors.lastname: Pinedo
authors.forename: Caroll J
authors.initials: CJ
authors.lastname: Beltrán
authors.forename: Carlos
authors.initials: C
authors.lastname: González
authors.forename: María-Julieta
authors.initials: MJ
authors.lastname: González
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Quera
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Hermoso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics / Q000276:immunology; D012995:Solubility; D046509:Tissue Culture Techniques; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*
chemical_list: C571163:CD33 protein, human; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D063268:Sialic Acid Binding Ig-like Lectin 3; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2