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Aberrant T-cell ont...
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Elgbratt, Kristina,1969Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
(author)
Aberrant T-cell ontogeny and defective thymocyte and colonic T-cell chemotactic migration in colitis-prone Galphai2-deficient mice
- Article/chapterEnglish2007
Publisher, publication year, extent ...
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Wiley,2007
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-13809
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-13809URI
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https://doi.org/10.1111/j.1365-2567.2007.02629.xDOI
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https://gup.ub.gu.se/publication/54165URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Galphai2-deficient mice, which spontaneously develop colitis, have previously been reported to have an increased frequency of mature, single positive thymocytes compared to wild-type mice. In this study we further characterized the intrathymic changes in these mice before and during overt colitis. Even before the onset of colitis, Galphai2(-/-) thymi weighed less and contained fewer thymocytes, and this was exacerbated with colitis development. Whereas precolitic Galphai2(-/-) mice had unchanged thymocyte density compared to Galphai2(+/-) mice of the same age, this was significantly decreased in mice with colitis. Thymic atrophy in Galphai2(-/-) mice involved mainly the cortex. Using a five-stage phenotypic characterization of thymocyte maturation based on expression of CD4, CD8, TCRalphabeta, CD69 and CD62L, we found that both precolitic and colitic Galphai2(-/-) mice had significantly increased frequencies of mature single-positive CD4(+) and CD8(+) medullary thymocytes, and significantly reduced frequencies and total numbers of immature CD4(+) CD8(+) double-positive thymocytes compared to Galphai2(+/-) mice. Furthermore, cortical and transitional precolitic Galphai2(-/-) thymocytes showed significantly reduced chemotactic migration towards CXCL12, and a trend towards reduced migration to CCL25, compared to wild-type thymocytes, a feature even more pronounced in colitic mice. This impaired chemotactic migration of Galphai2(-/-) thymocytes could not be reversed by increased chemokine concentrations. Galphai2(-/-) thymocytes also showed reduced expression of the CCL25 receptor CCR9, but not CXCR4, the receptor, for CXCL12. Finally, wild-type colonic lamina propria lymphocytes migrated in response to CXCL12, but not CCL25 and, as with thymocytes, the chemokine responsiveness was significantly reduced in Galphai2(-/-) mucosal lymphocytes.
Subject headings and genre
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Animal model
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Chemokines
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Mucosal inflammation
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Thymus
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Bjursten, Malin,1976Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xbjurm
(author)
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Willén, RogerUppsala universitet,Institutionen för genetik och patologi
(author)
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Bland, Paul William,1949Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xblapa
(author)
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Hultgren-Hörnquist, Elisabeth,1965Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xhorel
(author)
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Göteborgs universitetInstitutionen för biomedicin, avdelningen för mikrobiologi och immunologi
(creator_code:org_t)
Related titles
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In:Immunology: Wiley122:2, s. 199-2090019-28051365-2567
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