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  • 1.
    Elgbratt, Kristina
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Jansson, Andreas
    Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 5, artikel-id e36726Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.

  • 2.
    Elgbratt, Kristina
    et al.
    Örebro universitet, Hälsoakademin.
    Kurlberg, G.
    Dept Surg, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Hahn-Zohric, M.
    Dept Clin Immunol & Transfus Med, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Hälsoakademin. MIVAC Mucosal Immunobiol & Vaccine Ctr, Gothenburg Univ, Gothenburg, Sweden.
    Rapid migration of thymic emigrants to the colonic mucosa in ulcerative colitis patients2010Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 162, nr 2, s. 325-336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    P>Inflammatory bowel disease (IBD) is associated with imbalances of the local intestinal immune responses, with dysregulated CD4+ T cells contributing to the chronic inflammation. Having demonstrated altered T cell maturation in the thymus in two different mouse models of colitis, we set out to investigate whether abnormalities in T cell maturation is present in patients with ulcerative colitis (UC) or Crohn's disease (CD). Specimens were obtained from peripheral blood (CD; n = 14, UC; n = 22), colon and small intestinal specimens (CD; n = 6, UC; n = 13). As controls, peripheral blood specimens were obtained from healthy volunteers, patients with adenocarcinomas (n = 18) and colonic specimens from patients with adenocarcinomas (n = 14). Recent thymic emigrants were estimated by analysis of the normalized ratio of T cell receptor excision circles (TRECs) by real-time polymerase chain reaction (PCR). The frequency of naive- and proliferating T lymphocytes and markers of extrathymic T cell maturation in the mucosa was analyzed by flow cytometry and real time-PCR. TREC levels in peripheral blood T lymphocytes were similar between IBD patients and controls. In contrast, UC patients demonstrated significantly increased levels of TRECs both in intraepithelial and lamina propria lymphocytes from the colonic mucosa compared to patients with adenocarcinomas and CD. However, markers for extrathymic T cell maturation in the mucosa were not different between controls and IBD patients. The increased TREC levels in mucosal but not peripheral blood lymphocytes in UC patients in the absence of increased extrathymic maturation in situ in the mucosa together demonstrate that recent thymic emigrants are recruited rapidly to the inflamed mucosa of these patients.

  • 3.
    Kumawat, Ashok
    et al.
    Örebro universitet, Hälsoakademin.
    Elgbratt, Kristina
    Örebro universitet, Hälsoakademin.
    Bohr, Johan
    Örebro universitet, Hälsoakademin.
    Tysk, Curt
    Örebro universitet, Hälsoakademin.
    Hultgren Hörnquist, Elisabet
    Örebro universitet, Hälsoakademin.
    Increased frequencies of Ki67+ proliferating and CD45RO+ memory CD8+ and CD4+8+ T lymphocytes in the intestinal mucosa of collagenous colitis patients2011Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 73, nr 4, s. 374-374Artikel i tidskrift (Refereegranskat)
  • 4.
    Kumawat, Ashok Kumar
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Elgbratt, Kristina
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Örebro universitet, Hälsoakademin. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Region Örebro County, Örebro, sweden.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Reduced T cell receptor excision circle levels in the colonic mucosa of microscopic colitis patients indicate local proliferation rather than homing of peripheral lymphocytes to the inflamed mucosa2013Ingår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikel-id 408638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dysregulated T cell responses in the intestine may lead to chronic bowel inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC), together known as microscopic colitis (MC). Having demonstrated increased local T cell responses in the intestinal mucosa of MC patients, we investigated the recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic biopsies from CC (n = 8), LC (n = 5), and CC or LC patients in histopathological remission (CC-HR, n = 3) (LC-HR, n = 6), non-inflamed diarrhoea patients (n = 17), and controls (n = 10) by real-time PCR. We observed lower median TREC levels in both CC and LC patients as well as in LC-HR patients compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients presented with enhanced TREC levels compared to controls. None of the recorded differences did, however, reach statistical significance. A trend towards increased relative expression of CD3 was noted in all MC subgroups examined and reached statistical significance in LC patients compared to controls. In conclusion, reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67(+) T cells, suggests local expansion of resident T lymphocytes in the inflamed mucosa of MC patients.

  • 5.
    Kumawat, Ashok Kumar
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Elgbratt, Kristina
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Reduced T cell receptor excision circle (TREC) levels in the colonic mucosa of microscopic colitis patients indicate local proliferation rather than homing of peripheral lymphocytes to the inflamed mucosaManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Aims: Dysregulated T cell responses in the intestine may lead to chronic bowel inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC), together known as microscopic colitis (MC). Having demonstrated increased local T cell responses in the intestinal mucosa of MC patients, we investigated the recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients.

    Methods: Mucosal biopsies from CC (n=8), LC (n=5), and CC or LC patients in histopathological remission, (CC-HR, n=3), (LC-HR, n=6), non-inflamed diarrhoea patients (n=17) and controls (n=10) were analysed for TRECs expression by real time PCR.

    Results: The median TREC levels were lower in both CC and LC patients as well as in LCHR patients compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients presented with enhanced TREC levels compared to controls. None of the recorded differences did however reach statistical significance. No differences were observed in median TREC levels in either CC-HR or LC-HR patients compared to active CC and LC patients. A trend towards increased relative expression of CD3 was noted in all MC subgroups examined; and reached statistical significance in LC patients compared to controls. LC patients had ignificantly increased CD3 mRNA levels also compared to CC, CC-HR, LC-HR and non-inflamed iarrhoea patients.

    Conclusions: Reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67+ T cells, suggest local expansion of resident T lymphocytes in the inflamed mucosa of MC patients.

  • 6.
    Kumawat, Ashok Kumar
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Strid, Hilja
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Elgbratt, Kristina
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Microscopic colitis patients have increased frequencies of Ki67+proliferating and CD45RO+ active/memory CD8+ and CD4+8mucosal T cells2013Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 7, nr 9, s. 694-705Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.

    Methods: Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.

    Results: The proportions of CD8+ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO+CD8+ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4+8+ IELs and LPLs compared to controls. The proportions of CD45RO+ cells were increased in CD4+8+ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67+CD8+ IELs and LPLs compared to controls.

    In contrast, decreased proportions of CD4+ LPLs were observed in CC and LC as well as CD4+ IELs in LC compared to controls. Increased proportions of Ki67+CD4+ IELs and LPLs (p < 0.05) were observed in CC and LC patients. CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.

    Conclusion: LC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67+ and CD45RO+ CD8+ and CD4+8+ mucosal T cells.

  • 7. Welander, Edward
    et al.
    Åström, Maria
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    Enonge Fotabe, Leslie
    Kardeby, Caroline
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Tina, Elisabet
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Elgbratt, Kristina
    Örebro universitet, Institutionen för hälsovetenskaper.
    Pourlofti, Arvid
    Abawi, Akram
    Romild, Alma
    Kruse, Robert
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Repsilber, Dirk
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Crafoord, Jakob
    Ahlstrand, Erik
    Ivarsson, Mikael
    Örebro universitet, Institutionen för hälsovetenskaper.
    Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis2018Konferensbidrag (Refereegranskat)
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