Intestinal recruiting and activation profiles in peripheral blood mononuclear cells in response to pathogen‐associated molecular patterns stimulation in patients with IBS

Abstract

Background Immune activation, increased Toll‐like Receptors (TLR) expression, and gut epithelial diffusion of bacterial molecules have been reported in irritable bowel syndrome (IBS). Thus, we sought to relate these factors by analyzing gut homing (integrin α4β7), intestinal recruiting (CCR5) and activation (CD28) phenotypes, and the cytokines and chemokines concentration in peripheral blood T‐lymphocytes stimulated with TLR‐ligands. Methods Twenty‐one IBS‐Rome II (1 PI‐IBS) patients and 19 controls were studied. Isolated peripheral blood mononuclear cells were cultured with and without Escherichia coli lipopolysaccharide (LPS), Staphylococcus aureus peptidoglycan (PGN), and unmethylated cytosine‐phosphate‐guanine motifs (CpG). Phenotypes were investigated by flow cytometry and supernatant cytokines and chemokines were also measured. Key Results After LPS, CCR5 expression in CD4+ α4β7+ cells remained unchanged in IBS, but decreased in controls (p = 0.002), to lower levels than in IBS (Mean fluorescence intensity [MFI]: 1590 ± 126.9 vs 2417 ± 88.4, p < 0.001). There were less CD8+ α4β7+ CCR5+ cells (85.7 ± 1.5 vs 90.8 ± 0.9%, p = 0.006) after LPS and CD3+ α4β7+ CCR5+ (40.0 ± 1.7 vs 51.2 ± 4.3%, p = 0.006) after PGN in controls. Also, after LPS, CD28 decreased in CD4+ α4β7+ CCR5+ in IBS (MFI: 2337 ± 47.2 vs 1779 ± 179.2, p < 0.001), but not in controls. Cytokines and chemokines were similar, except for lower IL8/CXCL8 in the unstimulated condition in IBS (4.18, 95% CI: 3.94–4.42 vs 3.77, 3.59–3.95; p = 0.006). Conclusions & Inferences Pathogen‐associated molecular patterns stimulation of peripheral blood T cells expressing gut homing marker in IBS compared with controls resulted in an unsuccessful down‐regulation of the co‐expression of intestinal recruiting/residence phenotype and a state of activation. These findings support an interaction between an innate immune predisposition and microbial triggers, which may unleash or exacerbate IBS.

Modulators affecting the immune dialogue between human immune and colon cancer cells

“…In regard to the link between chronic inflammation and carcinogenesis, the mononuclear cells appear to be persuasive warriors expressing a vivid phagocytic capacity [14] , to encompass Toll-like receptors able to recognize pathogen molecules and to be capable to modulate both innate and adoptive immune responses [15][16][17] . Studies have shown that the number of Th1 and Th17 cells is increased in patients with inflammatory bowel disease and correlates well with its severity [18] , whereas the number of CD14 + and CCL11 + mononuclear cells has been found to be increased in colonic biopsies from patients with ulcerative colitis [19] .…”

IL-10 and TNF-&#945; polymorphisms in subjects with irritable bowel syndrome in Mexico

“…Secondly, we did not determine any differences between subjects with PI-IBS and those without a history of gastrointestinal infections as a triggering factor for IBS. However, it should be noted that PI-IBS frequency is very low in Mexico (35). We also did not rule out the presence of celiac disease or inflammatory bowel disease in these subjects, which could have modified the frequency of the polymorphisms studied.…”

Targeting the Integrin α4β7 with Probiotics and Nutraceuticals: A Working Hypothesis

“…14 Deregulated β7-mediated T lymphocytes homing was observed also in patients with gastrointestinal disorders, such as irritable bowel syndrome (IBS) [15][16][17] and functional dyspepsia. 18 Although these conditions impair patients' quality of life, nutritional interventions and/or functional foods (containing prebiotics, probiotics and/or nutraceuticals) rather than drug treatments should be recommended.…”