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Kumawat, Ashok KumarORCID iD iconorcid.org/0000-0002-2244-9816
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Publications (10 of 31) Show all publications
Kumawat, A. K., Yu, C., Mann, E. A., Schridde, A., Finnemann, S. C. & Mowat, A. M. (2018). Expression and characterization of αvβ5 integrin on intestinal macrophages. European Journal of Immunology, 48(7), 1181-1187
Open this publication in new window or tab >>Expression and characterization of αvβ5 integrin on intestinal macrophages
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2018 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 7, p. 1181-1187Article in journal (Refereed) Published
Abstract [en]

Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here we show for the first time that mature intestinal macrophages in mouse colon and small intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodelling of the extracellular matrix. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota. In adults, αvβ5 induces the differentiation of monocytes in response to the local environment and it confers intestinal macrophages with the ability to promote engulfment of apoptotic cells via engagement of the bridging molecule milk fat globule EGF-like molecule 8. In the absence of αvβ5, there are fewer monocytes in the mucosa and mature intestinal macrophages have decreased expression of metalloproteases and interleukin 10. Mice lacking αvβ5 on haematopoietic cells show increased susceptibility to chemical colitis and we conclude that αvβ5 contributes to the tissue repair by regulating the homeostatic properties of intestinal macrophages.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
Keywords
Homeostasis, Intestine, Macrophage, Phagocytosis, αvβ5 integrin
National Category
Immunology
Identifiers
urn:nbn:se:oru:diva-66706 (URN)10.1002/eji.201747318 (DOI)000437680700010 ()29676784 (PubMedID)2-s2.0-85049496311 (Scopus ID)
Note

Funding Agencies:

MRC UK  

Stiftelsen Olle Engkvist Byggmastare, Sweden  2014/27 

National Institutes of Health  R01-EY26215 

Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-07-25Bibliographically 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
Daferera, N., Kumawat, A. K., Hultgren-Hörnquist, E., Ignatova, S., Ström, M. & Münch, A. (2015). Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report. World Journal of Gastroenterology, 21(19), 6065-6071
Open this publication in new window or tab >>Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed) Published
Abstract [en]

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

Place, publisher, year, edition, pages
Pleasanton, USA: Baishideng Publishing Group Inc., 2015
National Category
Gastroenterology and Hepatology
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-55055 (URN)000355115600036 ()26019474 (PubMedID)2-s2.0-84929649035 (Scopus ID)
Note

Funding Agencies:

Abbott 

dr Falk Pharma 

Available from: 2017-01-30 Created: 2017-01-30 Last updated: 2017-11-29Bibliographically approved
Sundin, J., Rangel, I., Kumawat, A. K., Hultgren-Hörnquist, E. & Brummer, R. J. (2014). Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious irritable bowel syndrome patients. Scandinavian Journal of Gastroenterology, 49(9), 1068-1075
Open this publication in new window or tab >>Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious irritable bowel syndrome patients
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2014 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 9, p. 1068-1075Article in journal (Refereed) Published
Abstract [en]

Background: Irritable bowel syndrome (IBS) is characterized by chronic abdominal symptoms such as pain, discomfort, and altered bowel habits. A subset of IBS patients, denoted as post-infectious IBS (PI-IBS) patients, develop symptoms after an enteric infection. Distinct abnormalities in the gut mucosa, including mucosal inflammation, have been proposed to contribute to or be the cause of PI-IBS. This study investigated lymphocyte subsets in PI-IBS patients compared to healthy controls.

Materials and methods: Ten PI-IBS patients and nine healthy controls participated. All PI-IBS patients met the Rome III diagnostic criteria for IBS and reported sustained symptoms at least 1 year after an episode of acute gastroenteritis. Intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), isolated from mucosal tissue samples, were stained and analyzed for a comprehensive set of cell markers using flow cytometry.

Results: The number of LPLs in PI-IBS was significantly increased compared to those in healthy controls (p < 0.05). PI-IBS patients showed significantly increased proportions of CD45RO(+) CD4(+) activated/memory T cells (p < 0.05) and double-positive CD4(+) CD8(+) cells (p < 0.05), respectively, in the lamina propria. The number of CD19(+) LPLs was decreased in PI-IBS patients compared to healthy controls (p < 0.001).

Conclusion: This study presents new evidence that PI-IBS is associated with a sustained aberrant mucosal immune response and support future studies of anti-inflammatory or immune-modulating treatments in these patients.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
cell biology, gastrointestinal, infections, health economy, immunology
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-35383 (URN)10.3109/00365521.2014.926982 (DOI)000340829900006 ()24919810 (PubMedID)2-s2.0-84906318425 (Scopus ID)
Note

Funding Agency:

Medical Faculty, Örebro University

Available from: 2014-06-17 Created: 2014-06-17 Last updated: 2017-12-05Bibliographically 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: 2018-06-14Bibliographically 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: 2018-06-10Bibliographically approved
Kumawat, A. K. (2013). Adaptive immune response in the intestinal mucosa of microscopic colitis patients. (Doctoral dissertation). Örebro: Örebro universitet
Open this publication in new window or tab >>Adaptive immune response in the intestinal mucosa of microscopic colitis patients
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microscopic colitis (MC) is a chronic diarrhoeal disease of unknown aetiology, comprising collagenous colitis (CC) and lymphocytic colitis (LC). The nature of the adaptive local immune responses in the mucosa of MC patients is however far from elucidated. The present study investigates phenotypic and functional characteristics of the adaptive local immune responses in the colonic mucosa of these patients.

Our immunohistochemistry and flow cytometry studies (Paper I & II) demonstrated increased frequencies of CD8+ T cells in the colonic epithelium and lamina propria of both LC and CC patients compared to controls, whereas the frequencies of CD4+ T cells were unaltered or reduced. Our flow cytometry data revealed increased local activation of both CD4+ and CD8+ T cells in the lamina propria as well as the intraepithelial compartment of CC and LC patients compared to controls, demonstrated as increased proportions of these cells expressing the active/memory marker CD45RO and the proliferation marker Ki67.

Analysis of recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients revealed reduced TRECs levels in these patients compared to controls (Paper III). These results suggests that the observed increased numbers of T cells in the mucosa of CC and LC patients is due to the expansion of local resident T cells rather than direct recruitment of recent thymic emigrants to the mucosa.

Molecular analysis of T helper (Th) cell and cytotoxic T lymphocyte (Tc) mucosal cytokines at messenger and protein levels in the colonic biopsies from CC and LC patients demonstrated a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile and revealed significant differences in the mucosal cytokine levels in CC and LC patients compared to controls (Paper IV).

Finally, we have set up an in vitro model to investigate how the colonic milieu affects the activation and differentiation of T lymphocytes (Paper V). Our preliminary data indicate increased production of both pro inflammatory and antiinflammatory cytokines by peripheral blood T cells in the presence of soluble factors from the inflamed colonic mucosa of CC patients compared to controls.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 83
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 84
Keywords
Microscopic colitis, collagenous colitis, lymphocytic colitis, intraepithelial lymphocytes, lamina propria lymphocytes, T cell receptor excision circle, T helper cells, cytotoxic T lymphocyte and mucosal cytokines
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-27894 (URN)978-91-7668-929-5 (ISBN)
Public defence
2013-05-24, Hörsal P2, Prismahuset, Örebro universitet, Fakultetsgatan 1, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-03-18 Created: 2013-03-11 Last updated: 2017-10-17Bibliographically 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: 2018-02-07Bibliographically 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: 2018-05-21Bibliographically approved
Göranzon, C., Kumawat, A. K., Hultgren-Hörnqvist, E., Tysk, C., Eriksson, S., Bohr, J. & Nyhlin, N. (2013). Immunohistochemical characterization of lymphocytes in microscopic colitis. Journal of Crohn's and Colitis, 7(10), e434-e442
Open this publication in new window or tab >>Immunohistochemical characterization of lymphocytes in microscopic colitis
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2013 (English)In: Journal of Crohn's and Colitis, ISSN 1197-4982, Vol. 7, no 10, p. e434-e442Article in journal (Refereed) Published
Abstract [en]

Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry.

Methods Paraffin-embedded biopsies from 23 untreated patients with MC (CC = 13, LC = 10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP.

Results In CC and LC, an increase of predominantly CD8+ lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4+ lymphocytes was found in the lamina propria. CD45RO+ and Foxp3+ cells were more abundant in all areas in both patient groups compared to controls, as were CD20+ areas, although more scarce. Ki67+ areas were only more abundant in the epithelium, whereas CD30+ areas were more abundant in the lamina propria of both patient groups compared to controls.

Conclusions This study confirms an increased amount of CD8+ lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4+ lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s).

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Collagenous colitis, Lymphocytic colitis, Microscopic colitis, Lymphocytes, Immunohistochemistry
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-30117 (URN)10.1016/j.crohns.2013.02.007 (DOI)23523417 (PubMedID)2-s2.0-84884146798 (Scopus ID)
Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2018-05-19Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2244-9816

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