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A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development
Örebro universitet, Institutionen för hälsovetenskap och medicin.
Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
Örebro universitet, Institutionen för läkarutbildning.ORCID-id: 0000-0001-5460-8888
2012 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 5, artikkel-id e36726Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
San Francisco, USA: Public Library of Science , 2012. Vol. 7, nr 5, artikkel-id e36726
HSV kategori
Forskningsprogram
Biomedicin
Identifikatorer
URN: urn:nbn:se:oru:diva-24419DOI: 10.1371/journal.pone.0036726ISI: 000305336400031PubMedID: 22590596Scopus ID: 2-s2.0-84861002198OAI: oai:DiVA.org:oru-24419DiVA, id: diva2:544541
Forskningsfinansiär
Swedish Research CouncilKnowledge Foundation
Merknad

Funding Agencies:

Swedish Cancer Society 

Foundation of Professor Nanna Svartz

Örebro University 

Swedish Society of Medicine 

Tilgjengelig fra: 2012-08-15 Laget: 2012-08-15 Sist oppdatert: 2018-01-12bibliografisk kontrollert

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Elgbratt, KristinaHultgren-Hörnquist, Elisabeth

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