| 1. |
- Dige, A., et al.
(författare)
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Effects of Anti-TNFα Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease
- 2018
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2018
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Tidskriftsartikel (refereegranskat)abstract
- T helper 17 (Th17) cells produce interleukin (IL) 17-A. In addition, Th17 cells produce IL-21 and IL-22. Th17 cells have a disease-promoting role in Crohn’s disease (CD). We investigated the effects of anti-TNFα treatment on mucosal gene expression (qPCR) of IL-17A, IL-21, and IL-22 as well as on the frequency of lamina propria (LP) T cell subsets producing these cytokines (flow cytometry) in 12 active CD patients before and after 4 weeks of anti-TNFα treatment with adalimumab. At baseline, in inflamed mucosa we found increased gene expression of IL-17A and IL-22 but not IL-21 when compared to noninflamed mucosa. There were increased frequencies of IL-21-producing LP T cells but no differences in the frequencies of IL-17A- or IL-22-producing LP T cells when comparing inflamed versus noninflamed mucosa at baseline. There were no changes in the mucosal gene expression of IL-17A, IL-21, and IL-22 or the frequencies of IL-17A-, IL-21- and IL-22-producing LP T cell subsets between baseline and following 4 weeks of adalimumab initiation. Our results do not support the hypothesis that anti-TNFα treatment has an early effect on the mucosal levels of IL-17A, IL-21, and IL-22 or LP T cell production of these cytokines in CD.
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| 2. |
- Dige, A., et al.
(författare)
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Reduced numbers of mucosal DRint macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-alpha treatment in patients with Crohn's disease
- 2016
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:6, s. 692-699
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-TNF-alpha treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-alpha antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. Material and methods Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DRint and CD14 (+) DRhi MQs, CD141(+), CD141(-) and CD103(+ )DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry. Results At baseline, we observed higher numbers of DRint MQs and lower numbers of CD103(+ )DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 x 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DRint MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+ )DCs increased [9-20 x 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4. Conclusions In CD, mucosal inflammation is associated with high numbers of DRint MQs and low numbers of CD103(+ )DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-alpha treatment. These results suggest that DRint MQs play a pivotal role in CD inflammation.
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| 3. |
- Gorreja, Frida, et al.
(författare)
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Fecal Supernatants from Patients with Crohn's Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts
- 2024
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Ingår i: CELLS. - 2073-4409. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGF beta superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.
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| 4. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Macrophage and dendritic cell subsets in IBD: ALDH cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation
- 2016
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1935-3456 .- 1935-3456 .- 1933-0219. ; 9:1, s. 171-182
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Tidskriftsartikel (refereegranskat)abstract
- Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14- DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.
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| 5. |
- Niklasson, M., et al.
(författare)
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Are deficits in the equilibrium system relevant to the clinical investigation of solvent-induced neurotoxicity?
- 1997
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 23:3, s. 206-213
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The diagnosis of solvent-induced chronic toxic encephalopathy is commonly based on case histories of exposure to solvents, symptoms, and deficits on psychometric tests. It has previously been demonstrated that long-term solvent-exposed workers have disturbances of the equilibrium system. The correlation between these disturbances and the diagnosis of chronic toxic encephalopathy has been analyzed in the present study. MATERIAL AND METHODS: Sixty men, consecutively admitted due to the suspicion of this syndrome, were investigated and classified into 3 groups--solvent-induced chronic toxic encephalopathy, incipient chronic toxic encephalopathy and nonchronic toxic encephalopathy. They were all examined using an otoneurological test battery, including analysis of saccades, smooth pursuit, visual suppression of the vestibular ocular reflex, and dynamic posturography. RESULTS: Compared with healthy referents several of the subjects, even in the nonchronic toxic encephalopathy group, showed a reduced visual suppression ability, a prolonged latency of saccades, and pathological posturographic results. Some otoneurological tests correlated with the duration of exposure and the results of psychometric tests representing memory and perceptual skills. Nevertheless, there was no significant group correlation between the otoneurological findings and the diagnosis of chronic toxic encephalopathy. CONCLUSION: Disturbances revealed by an otoneurological investigation have so far not been considered in the diagnosis of chronic toxic encephalopathy. Our results indicate that an otoneurological test battery adds worthwhile information about lesions within the brainstem-cerebellar complex not revealed by a psychometric investigation.
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