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Hultgren, Olof
Alternative names
Publications (10 of 17) Show all publications
Gunaltay, S., Repsilber, D., Helenius, G., Nyhlin, N., Bohr, J., Hultgren, O. & Hultgren Hörnquist, E. (2017). Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis. Inflammatory Bowel Diseases, 23(6), 932-945
Open this publication in new window or tab >>Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
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2017 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed) Published
Abstract [en]

Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
Keywords
collagenous colitis, lymphocytic colitis, next-generation sequencing, ulcerative colitis, T-cell repertoire analysis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-59319 (URN)10.1097/MIB.0000000000001127 (DOI)000405609200014 ()28498152 (PubMedID)2-s2.0-85019705487 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation)  SLS-176271/2011  98031/2010 

Örebro University Hospital Research Foundation (Nyckelfonden)  

Research Committee, Örebro County Council  

Örebro University 

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2018-09-04Bibliographically approved
Günaltay, S., Ghiboub, M., Hultgren, O. & Hultgren Hörnquist, E. (2017). Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells. Digestive Diseases and Sciences, 62(5), 1204-1215
Open this publication in new window or tab >>Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells
2017 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 62, no 5, p. 1204-1215Article in journal (Refereed) Published
Abstract [en]

Background and Aim: Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model.

Methods: A colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR/Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid.

Results: The 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased.

Conclusions: Even a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
IL-37, Chemokines, CRISPR/Cas9
National Category
Immunology Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-54389 (URN)10.1007/s10620-016-4422-9 (DOI)000399814900016 ()28044228 (PubMedID)2-s2.0-85007553244 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation)  SLS-176271/2011  98031/2010 

Örebro University Hospital Research Foundation (Nyckelfonden)  

Örebro County Council Research Committee  

Örebro University 

Available from: 2017-02-07 Created: 2017-01-10 Last updated: 2018-07-30Bibliographically approved
Lange, A., Sundén-Cullberg, J., Magnuson, A. & Hultgren, O. (2017). Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality. PLoS ONE, 12(1), Article ID e0169176.
Open this publication in new window or tab >>Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169176Article in journal (Refereed) Published
Abstract [en]

Introduction and aims: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators.

Methods: 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study. Plasma concentrations of soluble BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) were measured with ELISA in serial blood samples. Comparisons were made with Mann-Whitney U test and correlations were assessed with Spearman's Rank correlation test. Cox proportional hazard models, with sBTLA and sPD-1 as fixed and sBTLA as time-varying covariates, were used to determine association with 28-day mortality.

Results: sBTLA levels were significantly higher in the sepsis cohort (median 14 ng/mL, IQR 8-29) compared to ICU controls (9 ng/mL, IQR 5-26, p = 0.048) and HC (2.9 ng/mL, IQR 0.9-9.1, p<0.01), and correlated to SOFA score. sBTLA levels were higher in 28 day sepsis non-survivors than in survivors (baseline median 28 ng/mL, IQR 13-41 vs 13 ng/mL, IQR 8-23, p = 0.04). After adjustment for age and comorbidities, the relative risk of 28 day mortality was nearly 5-fold higher in sepsis patients with a baseline sBTLA > 21 ng/mL, compared to those with a level below this threshold. sBTLA was even more associated with mortality in the time-varying analysis. sPD-1 levels were lower in the sepsis cohort compared to HC but not compared to ICU controls and were not associated with mortality. sCTLA-4 was detectable in only one subject.

Conclusion: Plasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-54384 (URN)10.1371/journal.pone.0169176 (DOI)000391639100023 ()28056053 (PubMedID)2-s2.0-85008970210 (Scopus ID)
Note

Funding Agencies:

Research Committee Region Örebro County

Nyckelfonden Region Örebro County

Olle Engkvist fund

Signe and Olof Wallenius trust

ALF

Karolinska University Hospital, Huddinge, Research Foundation

Available from: 2017-02-07 Created: 2017-01-10 Last updated: 2018-09-18Bibliographically approved
Gunaltay, S., Kumawat, A. K., Nyhlin, N., Bohr, J., Tysk, C., Hultgren, O. & Hultgren-Hörnquist, E. (2015). Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment. Mediators of Inflammation, Article ID 132458.
Open this publication in new window or tab >>Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
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2015 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed) Published
Abstract [en]

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

National Category
Cell and Molecular Biology Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-44605 (URN)10.1155/2015/132458 (DOI)000353128700001 ()2-s2.0-84928473938 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital Research Foundation (Nyckelfonden)

Research Committee, Orebro County Council

Örebro University

Available from: 2015-05-12 Created: 2015-05-12 Last updated: 2018-06-30Bibliographically approved
Kumawat, A. K., Nyhlin, N., Wickbom, A., Tysk, C., Bohr, J., Hultgren, O. & Hultgren-Hörnquist, E. (2014). An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4(+) T Cells. Mediators of Inflammation, Article ID 879843.
Open this publication in new window or tab >>An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4(+) T Cells
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2014 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 879843Article in journal (Refereed) Published
Abstract [en]

Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-gamma, IL-17A, IL-6, and IL-1 beta and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro-and anti-inflammatory cytokines.

Place, publisher, year, edition, pages
New York, USA: Hindawi Publishing Corporation, 2014
National Category
Cell and Molecular Biology Immunology in the medical area
Research subject
Immunology; Cell Research
Identifiers
urn:nbn:se:oru:diva-39815 (URN)10.1155/2014/879843 (DOI)000344673500001 ()25332518 (PubMedID)2-s2.0-84912000717 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation) SLS-176271/2011  98031/2010

Nyckelfonden at Örebro University Hospital

Örebro University Hospital Research Foundation

Lars Hierta Foundation

Available from: 2014-12-16 Created: 2014-12-16 Last updated: 2019-03-26Bibliographically approved
Günaltay, S., Nyhlin, N., Kumawat, A. K., Tysk, C., Bohr, J., Hultgren, O. & Hultgren-Hörnquist, E. (2014). Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis. World Journal of Gastroenterology, 20(34), 12249-12259
Open this publication in new window or tab >>Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
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2014 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 34, p. 12249-12259Article in journal (Refereed) Published
Abstract [en]

AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Place, publisher, year, edition, pages
WJG Press, 2014
Keywords
Interleukin-37, MicroRNA, Lymphocytic colitis, Collagenous colitis, Ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-37676 (URN)10.3748/wjg.v20.i34.12249 (DOI)000341719100033 ()2-s2.0-84909606787 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council

Örebro University

Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2019-03-26Bibliographically approved
Gunaltay, S., Ghiboub, M., Hultgren, O. & Hultgren-Hörnquist, E. (2014). The role of IL-37 on cytokine responses downstream of TLR4 and TLR5 signalling in intestinal epithelial cells. Immunology, 143, 94-95
Open this publication in new window or tab >>The role of IL-37 on cytokine responses downstream of TLR4 and TLR5 signalling in intestinal epithelial cells
2014 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 143, p. 94-95Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-40157 (URN)000345702600261 ()
Available from: 2015-01-08 Created: 2015-01-07 Last updated: 2018-02-07Bibliographically approved
Kumawat, A., Tysk, C., Bohr, J., Hultgren, O. & Hultgren-Hörnquist, E. (2013). An in vitro model for analysis of the impact of the colonic milieu in collagenous colitis patients on peripheral T lymphocyte activation and differentiation. Paper presented at Annual Congress of the British-Society-for-Immunology, Liverpool, ENGLAND, DEC 02-05, 2013. Immunology, 140, 168-168
Open this publication in new window or tab >>An in vitro model for analysis of the impact of the colonic milieu in collagenous colitis patients on peripheral T lymphocyte activation and differentiation
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2013 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 168-168Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2013
National Category
Medical and Health Sciences Immunology
Identifiers
urn:nbn:se:oru:diva-32912 (URN)000327487700440 ()
Conference
Annual Congress of the British-Society-for-Immunology, Liverpool, ENGLAND, DEC 02-05, 2013
Available from: 2014-01-03 Created: 2014-01-03 Last updated: 2019-03-26Bibliographically approved
Selden, A. I., Calo, A., Molleby, G. & Hultgren, O. (2013). Chironomid midge sensitization in sewage workers: case study. Medical and Veterinary Entomology, 27(3), 346-348
Open this publication in new window or tab >>Chironomid midge sensitization in sewage workers: case study
2013 (English)In: Medical and Veterinary Entomology, ISSN 0269-283X, E-ISSN 1365-2915, Vol. 27, no 3, p. 346-348Article in journal (Refereed) Published
Abstract [en]

Non-biting chironomid midges (Diptera: Chironomidae) may cause sensitization and allergic reactions in humans and have recently been identified as a potential health problem in Swedish municipal sewage treatment plants. To investigate, on a pilot scale, the allergenic potential of chironomids in sewage workers, all workers (n = 8) at a sewage treatment plant and local controls (n = 16) completed a symptom questionnaire, underwent measurement of the fraction of nitric oxide in exhaled air, spirometry, and provided serum samples for the determination of atopy status and the prevalence of specific immunoglobulin E (IgE) antibodies against Chironomus thummi (Chi t) using a commercial fluorescence enzyme immunoassay (FEIA). Three sewage workers (38%) but no controls (0%) were FEIA positive for C. thummi-specific IgE antibodies (P < 0.05). No other health-related findings were significantly different between the groups. The study suggested that occupational exposure to Chironomids may cause sensitization with circulating IgE-antibodies in sewage workers.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2013
Keywords
Chironomus thummi, fluorescence enzyme immunoassay, IgE, sensitization, sewage treatment, sewage workers
National Category
Medical and Health Sciences Veterinary Science
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-30725 (URN)10.1111/j.1365-2915.2012.01058.x (DOI)000322992400012 ()23734859 (PubMedID)2-s2.0-84881611985 (Scopus ID)
Available from: 2013-09-06 Created: 2013-09-06 Last updated: 2018-05-21Bibliographically approved
Gunaltay, S., Nyhlin, N., Kumawat, A., Tysk, C., Bohr, J., Hultgren, O. & Hultgren-Hörnquist, E. (2013). IL-1/TLR signaling inhibitors in microscopic and ulcerative colitis: Immunopathogenic markers of active disease and remission. Paper presented at Annual Congress of the British-Society-for-Immunology, DEC 02-05, 2013, Liverpool, ENGLAND. Immunology, 140, 167-167
Open this publication in new window or tab >>IL-1/TLR signaling inhibitors in microscopic and ulcerative colitis: Immunopathogenic markers of active disease and remission
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2013 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 167-167Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-32911 (URN)000327487700438 ()
Conference
Annual Congress of the British-Society-for-Immunology, DEC 02-05, 2013, Liverpool, ENGLAND
Available from: 2014-01-03 Created: 2014-01-03 Last updated: 2019-03-26Bibliographically approved
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