| 1. |
- Alfredsson, Johannes, et al.
(författare)
-
Isobaric labeling-based quantitative proteomics of FACS-purified immune cells and epithelial cells from the intestine of Crohn's disease patients reveals proteome changes of potential importance in disease pathogenesis.
- 2023
-
Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 23:5
-
Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease (CD) is a chronic condition characterized by recurrent flares of inflammation in the gastrointestinal tract. Disease etiology is poorly understood and is characterized by dysregulated immune activation that progressively destroys intestinal tissue. Key cellular compartments in disease pathogenesis are the intestinal epithelial layer and its underlying lamina propria. While the epithelium contains predominantly epithelial cells, the lamina propria is enriched in immune cells. Deciphering proteome changes in different cell populations is important to understand CD pathogenesis. Here, using isobaric labeling-based quantitative proteomics, we perform an exploratory study to analyze in-depth proteome changes in epithelial cells, immune cells and stromal cells in CD patients compared to controls using cells purified by FACS. Our study revealed increased proteins associated with neutrophil degranulation and mitochondrial metabolism in immune cells of CD intestinal mucosa. We also found upregulation of proteins involved in glycosylation and secretory pathways in epithelial cells of CD patients, while proteins involved in mitochondrial metabolism were reduced. The distinct alterations in protein levels in immune- versus epithelial cells underscores the utility of proteome analysis of defined cell types. Moreover, our workflow allowing concomitant assessment of cell-type specific changes on an individual basis enables deeper insight into disease pathogenesis.
|
|
| 2. |
- Gorreja, Frida, et al.
(författare)
-
MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn ' s Disease Patients
- 2022
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 45, s. 1631-1650
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammasomes are intracellular protein complexes whose activation results in proinflammatory cytokines. Inflammasomes are implicated in Crohn ' s disease (CD) pathogenesis, yet the contribution of inflammasomes in intestinal epithelial cells (IECs) versus lamina propria (LP) macrophages is poorly understood. Whether inflammasome expression in intestinal tissue reflects the serum inflammatory protein profile of patients is also not known. We aimed to determine the intestinal cell types where inflammasome expression is increased in CD and if they correlate with the serum protein profile. RT-PCR and NanoString nCounter technology were used to characterize inflammasome gene expression in CD patients and controls. The mucosa, LP and IEC cell fractions and FACS-sorted cells were analyzed. Proximity extension assay with a 92-protein panel was used to determine the serum inflammatory protein profile. Compositional analysis was used to correlate ileum inflammasome gene expression with intestinal mononuclear phagocyte populations. We show that NLRP3 and MEFV inflammasome sensors and downstream effector expression including IL-1 beta are increased in inflamed mucosa of IBD patients and correlate with disease activity. Inflammasome gene expression increased with the abundance of immature intestinal macrophages, and increased IL-1 beta released by CD LP cells correlated with immature macrophage frequency. Inflammasome gene expression was also increased in circulating monocytes, the precursors of immature intestinal macrophages. Finally, the serum inflammatory profile of CD patients correlates with ileal expression of genes related to NLRP3 and MEFV inflammasomes. Overall, we show that MEFV and NLRP3 inflammasome expression in CD intestine is attributed to the accumulation of immature macrophages and correlates with serum inflammatory proteins.
|
|
| 3. |
- Graf, Wilhelm, et al.
(författare)
-
Long-term outcome after surgery for Crohn's anal fistula
- 2016
-
Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 18, s. 80-85
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: Treatment of Crohn's anal fistula remains challenging and little is known about factors associated with healing. The aim of this study was to assess the rate of healing after surgical treatment and analyse clinical variables related to healing.METHOD: 119 patients (63 female, mean age 36 (±13.7) years with histopathologically verified Crohn's disease underwent a surgical procedure for anal fistula at four main referral centres in Sweden, January 1998 - December 2009. Baseline and treatment-related variables were recorded and analysed for correlation with fistula healing at a final follow-up at a mean 7.2 (median 7.1, 1.0-17.5) years.RESULTS: Of the 119 patients 62 (52%) were healed at final follow-up. Fourteen healed after one procedure and the remaining 48 healed after a further median of 4.0 (2-20) procedures. Ten (8%) patients were subjected to a proctectomy. Final healing was more common in patients operated with a procedure aiming at eradicating the fistula (P=0.0001), without proctitis (P=0.02), and a shorter duration of Crohn' disease (P=.0019).CONCLUSION: Long-term healing of a Crohn's anal fistula can be expected in about half of the patients, usually after repeated surgical treatment. The probability for cure was higher when a curative operation was performed in a patient without proctitis and a shorter duration of Crohn's disease. An attempt to close a Crohn's anal fistula is thus often worthwhile. This article is protected by copyright. All rights reserved.
|
|
| 4. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
Macrophage and dendritic cell subsets in IBD: ALDH cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation
- 2016
-
Ingår i: Mucosal Immunology. - : Elsevier BV. - 1935-3456 .- 1935-3456 .- 1933-0219. ; 9:1, s. 171-182
-
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.
|
|
| 5. |
- Ahlmanner, Filip, et al.
(författare)
-
CD39+ regulatory T cells accumulate in colon adenocarcinomas and display markers of increased suppressive function
- 2018
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:97, s. 36993-37007
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing knowledge of the function and regulation of tumor-infiltrating lymphocytes has led to new insights in cancer immunotherapy. Regulatory T cells (Treg) accumulate in colon tumors, and we recently showed that CD39+ Treg from cancer patients inhibit transendothelial migration of conventional T cells. CD39 mediates the hydrolysis of ATP to immunosuppressive adenosine and adds to the immunosuppressive effects of Treg. Here, we further investigated the regulatory features of intratumoral CD39+ Treg in colon cancer. Using flow cytometry analyses of cells from 46 colon cancer patients, we confirm the accumulation of CD39+ Treg in the tumor tissue compared to unaffected colon tissue, and also show that tumor-infiltrating Treg express more CD39 and Foxp3 on a per cell basis. Furthermore, CD39+ Treg in tumors express markers indicating increased turnover and suppressive ability. In particular, tumor-infiltrating CD39+ Treg have high expression of surface molecules related to immunosuppression, such as ICOS, PD-L1 and CTLA-4. Functional suppression assays also indicate potent suppressive capacity of CD39+ Treg on proliferation and IFN-γ secretion by conventional T cells. In conclusion, our results identify tumor-infiltrating CD39+ Treg as a numerous and potentially important immunosuppressive subset, and suggest that immunotherapy aimed at reducing the activity of CD39+ Treg may be particularly useful in the setting of colon cancer. © 2018 Ahlmanner et al.
|
|
| 6. |
|
|
| 7. |
- Andreasson, Jakob, 1975, et al.
(författare)
-
Electron-lattice interactions in the perovskite LaFe0.5Cr0.5O3 characterized by optical spectroscopy and LDA plus U calculations
- 2009
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 80:7, s. 075103-
-
Tidskriftsartikel (refereegranskat)abstract
- We use resonance Raman scattering (incident photon energies between 1.8 and 4.13 eV), LDA+U calculations, spectroscopic ellipsometry, and oblique IR reflectivity to characterize the strong electron-phonon interactions in the disordered perovskite LaFe0.5Cr0.5O3. When the photon energy coincides with a Cr to Fe Mott-Hubbard transfer gap around 2.4 eV the electron-phonon interaction is manifested by a Franck-Condon effect with exceptional first-and higher order scattering of a local oxygen breathing mode. At higher incident energies we observe a superposition of Franck-Condon scattering and Frohlich interaction induced infrared active longitudinal optical two-phonon scattering activated mainly by O to Fe charge transfer. Our results establish LaFe0.5Cr0.5O3 as a model compound for research on electron-phonon interactions in strongly correlated complex systems and show that Franck-Condon scattering in complex solids is not limited to Jahn-Teller active compounds.
|
|
| 8. |
- Andreasson, Jakob, 1975, et al.
(författare)
-
Electron-phonon interactions in perovskites containing Fe and Cr studied by Raman scattering using oxygen-isotope and cation substitution
- 2008
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 78:23, s. 235103-
-
Tidskriftsartikel (refereegranskat)abstract
- We use temperature-dependent inelastic light scattering to study the origin of the strong multiphonon scattering of a local oxygen breathing mode present in the mixed B-site orthorhombic (space group Pnma) perovskite LaFe0.5Cr0.5O3 but absent in isostructural LaFeO3 and LaCrO3. It is seen that the multiphonon scattering is critically sensitive to the presence of both Fe and Cr ions on the B site. These results support our interpretation that the multiphonon scattering is activated by local electron-phonon interactions according to the Franck-Condon picture following an Fe-Cr charge transfer. Further, O-18 substitution is performed on the x=0, 0.04, and 0.5 compounds and clearly shows that all modes appearing above the first-order phonon-scattering region in these compounds originate from higher-order oxygen stretching vibrations. In particular this is the case for the strong second-order scattering dominating the scattering response in LaFeO3. Accordingly we propose that these modes are generated by infrared-active longitudinal optical (IR LO) two-phonon and combination scattering activated by Frohlich interaction. For x=0.02 and 0.04 the characteristic IR LO two-phonon and Franck-Condon multiphonon-scattering profiles mix. We also study the influence of isovalent cation substitution and Sr doping in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) and La1-ySryFe0.5Cr0.5O3-delta (y=0, 0.16, and 0.5) on the strong electron-phonon coupling present in LaFe0.5Cr0.5O3. The Franck-Condon effect in LaFe0.5Cr0.5O3, is not significantly affected by isovalent A-site substitution, despite the increasing orthorhombic distortion associated with decreasing A-site ionic radii. On the contrary, aliovalent Sr doping causes a rapid decrease in the Franck-Condon scattering. This shows that the strong electron-phonon coupling in these compounds is highly sensitive to local lattice and electronic decoherence but insensitive to global lattice distortions. Finally, a preliminary assignment of the A(g) and B-2g phonon modes in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) is made based on the present observations and published results for LaCrO3 and AMnO(3). The modes associated with oxygen octahedral tilt and bending vibrations are heavily influenced by the magnitude of the orthorhombic distortion.
|
|
| 9. |
- Andreasson, Jakob, 1975, et al.
(författare)
-
Franck-Condon higher order lattice excitations in the LaFe(1-x)Cr(x)O3 (x=0, 0.1, 0.5, 0.9, 1.0) perovskites due to Fe-Cr charge transfer effects
- 2007
-
Ingår i: Physical Review B. ; 75, s. 104302-
-
Tidskriftsartikel (refereegranskat)abstract
- First and higher order lattice excitiations in the B-site disordered perovskites LaFe(1-x)Cr(x)O3 (x = 0, 0.1, 0.5, 0.9, 1) and La(0.835)Sr(0.165)Fe(0.5)Cr(0.5)O(3-d) are investigated using temperature dependent and polarised inelastic light scattering [lambda = 515 nm (2.41 eV) and 676 nm (1.83 eV)] on oriented crystallites.A peak at approximately 2.4 eV in the imaginary part of the dielectric function of LaFe(0.5)Cr(0.5)O3 is assigned to a charge transfer from Fe 3+ (d5) to Cr 3+ (d3) ions and coupled the appearance of an intense Ag-like mode at approximately 700 cm-1 in the Raman data. This excitation is identified as a symmetric oxygen breathing mode activated by the Fe-Cr charge transfer through an orbital coupling mechanism. Higher order scattering (up to 7th order) of the intrinsic Raman active symmetric breathing mode is also explained by an orbital mediated, electron-phonon coupling, similar to the Franck-Condon effect observed in the Jahn-Teller active perovskite structured manganite LaMnO3. These results show that the Franck-Condon mechanism is a more common mechanism for resonant higher order scattering in solids than previously believed and propose the LaFe(1-x)Cr(x)O(3) system as a model system for electron-phonon coupling and higher order Raman scattering in solids.
|
|
| 10. |
- Bengtsson, Jonas, 1961, et al.
(författare)
-
Can a failed ileal pouch anal anastomosis be left in situ?
- 2007
-
Ingår i: Colorectal disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 9:6, s. 503-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.
|
|
