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Hammarström, Marie-Louise
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Publications (10 of 89) Show all publications
Simonyté Sjödin, K., Hammarström, M.-L., Rydén, P., Sjödin, A., Hernell, O., Engstrand, L. & West, C. E. (2019). Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age. Allergy. European Journal of Allergy and Clinical Immunology, 74(1), 176-185
Open this publication in new window or tab >>Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age
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2019 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, no 1, p. 176-185Article in journal (Refereed) Published
Abstract [en]

Background: Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.

Methods: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.

Results: At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacteriumand depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year-olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).

Conclusions: We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
allergy, diversity, intestinal colonization, microbiome, T-cell response
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-157612 (URN)10.1111/all.13485 (DOI)000459664100017 ()29786876 (PubMedID)
Available from: 2019-03-27 Created: 2019-03-27 Last updated: 2019-03-27Bibliographically approved
AbdelMageed, M., Ali, H., Ohlsson, L., Lindmark, G., Hammarström, M.-L., Hammarström, S. & Sitohy, B. (2019). The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome. International Journal of Molecular Sciences, 20(22), Article ID 5793.
Open this publication in new window or tab >>The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 22, article id 5793Article in journal (Refereed) Published
Abstract [en]

hemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
chemokines, CXCL17, CEA, EpCAM, qRT-PCR, immunohistochemistry, immunomorphometry
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-167031 (URN)10.3390/ijms20225793 (DOI)000502786800275 ()31752131 (PubMedID)
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-09Bibliographically approved
Bitar, A., Aung, K. M., Wai, S. N. & Hammarström, M.-L. (2019). Vibrio cholerae derived outer membrane vesicles modulate the inflammatory response of human intestinal epithelial cells by inducing microRNA-146a. Scientific Reports, 9, Article ID 7212.
Open this publication in new window or tab >>Vibrio cholerae derived outer membrane vesicles modulate the inflammatory response of human intestinal epithelial cells by inducing microRNA-146a
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7212Article in journal (Refereed) Published
Abstract [en]

The small intestinal epithelium of Vibrio cholerae infected patients expresses the immunomodulatory microRNAs miR-146a and miR-155 at acute stage of disease. V. cholerae release outer membrane vesicles (OMVs) that serve as vehicles for translocation of virulence factors including V. cholerae cytolysin (VCC). The aim was to investigate whether OMVs, with and/or without VCC-cargo could be responsible for induction of microRNAs in intestinal epithelial cells and thereby contribute to immunomodulation. Polarized tight monolayers of T84 cells were challenged with OMVs of wildtype and a VCC deletion mutant of the non-O1/non-O139 (NOVC) V. cholerae strain V:5/04 and with soluble VCC. OMVs, with and without VCC-cargo, caused significantly increased levels of miR-146a. Increase was seen already after 2 hours challenge with OMVs and persisted after 12 hours. Challenge with soluble VCC caused significant increases in interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), CCL20, IL-1β, and IRAK2 mRNA levels while challenge with OMVs did not cause increases in expression levels of any of these mRNAs. These results suggest that V. cholerae bacteria release OMVs that induce miR-146a in order to pave the way for colonization by reducing the strength of an epithelial innate immune defence reaction and also preventing inflammation in the mucosa that factors like VCC can evoke.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-159266 (URN)10.1038/s41598-019-43691-9 (DOI)000467543700027 ()31076615 (PubMedID)2-s2.0-85065655754 (Scopus ID)
Available from: 2019-05-23 Created: 2019-05-23 Last updated: 2019-06-19Bibliographically approved
Alhouayek, M., Gouveia-Figueira, S., Hammarström, M.-L. & Fowler, C. J. (2018). Involvement of CYP1B1 in interferon gamma-induced alterations of epithelial barrier integrity. British Journal of Pharmacology, 175(6), 877-890
Open this publication in new window or tab >>Involvement of CYP1B1 in interferon gamma-induced alterations of epithelial barrier integrity
2018 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 175, no 6, p. 877-890Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE CYP1B1 and CYP1A1 are important extra-hepatic cytochromes, expressed in the colon and involved in the metabolism of dietary constituents and exogenous compounds. CYP1B1 expression is increased by pro-inflammatory cytokines, and it has been recently implicated in regulation of blood brain barrier function. We investigated its involvement in the increased permeability of the intestinal epithelial barrier observed in inflammatory conditions. EXPERIMENTAL APPROACH Epithelial monolayers formed by human T84 colon carcinoma cells cultured on transwells, were disrupted by incubation with IFN gamma (10 ng.mL(-1)). Monolayer integrity was measured using transepithelial electrical resistance. CYP1A1 and CYP1B1 inhibitors or inducers were applied apically. Potential mechanisms of action were investigated using RT-qPCR. KEY RESULTS IFN gamma disrupts the barrier integrity of the T84 monolayers and increases CYP1B1 and HIF1 alpha mRNA expression. CYP1B1 induction is inhibited by the NF-kappa B inhibitor ammonium pyrrolidinedithiocarbamate (100 mu M) but not by the HIF1 alpha inhibitor 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (50 mu M). Inhibition of CYP1B1 with the selective inhibitor 2,4,3,5-tetramethoxystilbene (100 nM) partly reverses the effects of IFN gamma on epithelial permeability. CONCLUSIONS AND IMPLICATIONS These data suggest that increased expression of CYP1B1 is involved in the effects of IFN gamma on epithelial permeability. Inhibition of CYP1B1 counteracts the alterations of epithelial barrier integrity induced by IFN gamma and could thus have a therapeutic potential in disorders of intestinal permeability associated with inflammation.

Place, publisher, year, edition, pages
WILEY, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-145774 (URN)10.1111/bph.14122 (DOI)000426126500002 ()29232759 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2019-11-20Bibliographically approved
Rashad, Y., Olsson, L., Israelsson, A., Öberg, Å., Lindmark, G., Hammarström, M.-L., . . . Sitohy, B. (2018). Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer. Tumor Biology, 40(9), Article ID 1010428318799251.
Open this publication in new window or tab >>Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer
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2018 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 40, no 9, article id 1010428318799251Article in journal (Refereed) Published
Abstract [en]

Lymph node metastasis is the most important prognostic characteristic of colorectal cancer. Carcinoembryonic antigen messenger RNA was shown to detect tumor cells that have disseminated to lymph nodes of colorectal cancer patients and to be at least as good as the hematoxylin and eosin method to predict survival in colorectal cancer patients. CXCL17 was recently shown to be ectopically expressed in colon cancer tumors. Therefore, CXCL17 may serve as prognostic marker alone or in combination with carcinoembryonic antigen. CXCL17 and carcinoembryonic antigen messenger RNA levels were determined using quantitative reverse transcription polymerase chain reaction with RNA copy standard in 389 lymph nodes of 120 colon cancer patients (stages I–IV) and 67 lymph nodes of 12 control patients with inflammatory bowel disease as well as in 68 primary tumors and 30 normal colon tissue samples. Lymph nodes of colon cancer patients were analyzed for CXCL17 and carcinoembryonic antigen protein expression by immunohistochemistry. CXCL17 messenger RNA was expressed in primary tumors at high levels, while it was barely detected in normal colon tissue (p < 0.0001). Similarly, CXCL17 messenger RNA levels were significantly higher in hematoxylin- and eosin-positive (hematoxylin and eosin (+)) lymph nodes compared to hematoxylin- and eosin-negative nodes (p < 0.0001). CXCL17 messenger RNA levels were investigated in lymph nodes grouped according to carcinoembryonic antigen messenger RNA levels: low (–), intermediate (int), and high (+). CXCL17 messenger RNA levels were higher in the carcinoembryonic antigen (int) and carcinoembryonic antigen (+) groups compared to the carcinoembryonic antigen (−) group (p = 0.03 and p < 0.0001, respectively). In lymph nodes of stage III and IV patients, CXCL17 messenger RNA levels correlated with carcinoembryonic antigen messenger RNA levels (p < 0.0001, r = 0.56 and p = 0.0002, r = 0.66, respectively). Staining of consecutive lymph node sections for CXCL17 and carcinoembryonic antigen demonstrated that the same cells expressed both proteins. Altogether, these results indicate that CXCL17 in lymph nodes is expressed by tumor cells. Patients were grouped according to the CXCL17 mRNA levels in the highest lymph node with low levels (−) and high levels (+). CXCL17(+) CC patients showed 2.2 fold increased risk for recurrence (P = 0.03) and decreased mean disease-free survival time of 33 months compared to CXCL17(−) CC patients (P = 0.03). CXCL17(+) carcinoembryonic antigen (int) colon cancer patients showed increased risk for recurrence by 8.3 fold (p = 0.04) and decreased mean disease-free survival time of 46 months compared to CXCL17(−) carcinoembryonic antigen (int) colon cancer patient at follow-up after 12 years (p = 0.02). The presence of tumor cells expressing CXCL17 in regional lymph nodes is a sign of poor prognosis. Analysis of CXCL17 messenger RNA is particularly useful to detect less differentiated colon cancer tumors expressing relatively low carcinoembryonic antigen messenger RNA levels. Thus, CXCL17 messenger RNA in combination with carcinoembryonic antigen messenger RNA may be used as a complementary tool to the hematoxylin and eosin method for detection of poorly differentiated, aggressive tumors.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
CXCL17, carcinoembryonic antigen, cumulative survival curve, disseminated tumor cells, recurrence risk
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-159263 (URN)10.1177/1010428318799251 (DOI)30198422 (PubMedID)2-s2.0-85054132105 (Scopus ID)
Available from: 2019-05-23 Created: 2019-05-23 Last updated: 2019-06-14Bibliographically approved
Pietz, G., De, R., Hedberg, M., Sjöberg, V., Sandström, O., Hernell, O., . . . Hammarström, M.-L. (2017). Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells. PLoS ONE, 12(9), Article ID e0185025.
Open this publication in new window or tab >>Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, article id e0185025Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-139860 (URN)10.1371/journal.pone.0185025 (DOI)000411339900076 ()28934294 (PubMedID)
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-06-09Bibliographically approved
Bitar, A., De, R., Melgar, S., Aung, K. M., Rahman, A., Qadri, F., . . . Hammarström, M.-L. (2017). Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera. PLoS ONE, 12(3), Article ID 0173817.
Open this publication in new window or tab >>Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id 0173817Article in journal (Refereed) Published
Abstract [en]

The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (P<0.009 versus controls; P = 0.03 versus convalescent stage, pairwise). Both microRNAs were mainly expressed in the epithelium. Only marginal down-regulation of target genes IRAK1 and CARD10 was seen and a weak cytokine-profile was identified in the acute infected mucosa. No elevation of microRNA levels was seen in ETEC infection. Challenge of tight monolayers with the wild type V. cholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (P<0.01). One clinical isolate caused reduction in IRAK1 levels (P<0.05) and none of the strains induced inflammatory cytokines. In contrast, secreted factors from these strains caused markedly increased levels of IL-8, IL-1β, and CARD10 (P<0.001), without inducing microRNA expression. Thus, miR-146a and miR-155 are expressed in the duodenal epithelium at the acute stage of cholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation evoked by its own secreted factors, thereby decreasing the risk of being eliminated.

National Category
Microbiology in the medical area Immunology
Identifiers
urn:nbn:se:umu:diva-133013 (URN)10.1371/journal.pone.0173817 (DOI)000398945800031 ()28319200 (PubMedID)
Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-06-09Bibliographically approved
Ohlsson, L., Hammarström, M.-L., Lindmark, G., Hammarström, S. & Sitohy, B. (2016). Ectopic expression of the chemokine CXCL17 in colon cancer cells. British Journal of Cancer, 114(6), 697-703
Open this publication in new window or tab >>Ectopic expression of the chemokine CXCL17 in colon cancer cells
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2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 6, p. 697-703Article in journal (Refereed) Published
Abstract [en]

Background: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development. Methods: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT-PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry. Results: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P<0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P = 0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10-and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17. Conclusions: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients.

Keywords
CXCL17, CXCL10, CXCL9, CCL2, colon cancer, prognosis, immunomorphometry, qRT-PCR
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-119285 (URN)10.1038/bjc.2016.4 (DOI)000372523500013 ()26889977 (PubMedID)
Available from: 2016-05-16 Created: 2016-04-15 Last updated: 2018-06-07Bibliographically approved
Sjöberg, V., Hollén, E., Pietz, G., Magnusson, K.-E., Fälth-Magnusson, K., Sundström, M., . . . Hammarström, M.-L. (2014). Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease. Clinical and Translational Gastroenterology, 5, Article ID e58.
Open this publication in new window or tab >>Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease
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2014 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 5, article id e58Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.

METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.

RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).

CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.

National Category
Basic Medicine Pediatrics
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-93052 (URN)10.1038/ctg.2014.9 (DOI)000355530800002 ()24964993 (PubMedID)2-s2.0-84903278030 (Scopus ID)
Available from: 2014-09-11 Created: 2014-09-11 Last updated: 2018-06-07Bibliographically approved
Sjöberg, V., Sandström, O., Hedberg, M., Hammarström, S., Hernell, O. & Hammarström, M.-L. (2013). Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria. PLoS ONE, 8(1), e53414
Open this publication in new window or tab >>Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, p. e53414-Article in journal (Refereed) Published
Abstract [en]

A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the "Swedish CD epidemic" and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8(+) T cells (Tc17) and CD4(+) T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.

Place, publisher, year, edition, pages
PLoS, Public Library of Science, 2013
National Category
Pediatrics Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-64525 (URN)10.1371/journal.pone.0053414 (DOI)000313551500069 ()23326425 (PubMedID)
Available from: 2013-01-31 Created: 2013-01-31 Last updated: 2018-06-08Bibliographically approved
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