Aberrant T-cell ontogeny and defective thymocyte and colonic T-cell chemotactic migration in colitis-prone Galphai2-deficient mice

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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

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Wiley,2007
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LIBRIS-ID:oai:DiVA.org:uu-13809
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-13809URI
https://doi.org/10.1111/j.1365-2567.2007.02629.xDOI
https://gup.ub.gu.se/publication/54165URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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

Animal model
Chemokines
Mucosal inflammation
Thymus
MEDICINE
MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

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)
Willén, RogerUppsala universitet,Institutionen för genetik och patologi (author)
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)
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)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för mikrobiologi och immunologi (creator_code:org_t)

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In:Immunology: Wiley122:2, s. 199-2090019-28051365-2567

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