Loss of Gαi proteins impairs thymocyte development, disrupts T-cell trafficking, and leads to an expanded population of splenic CD4+PD-1+CXCR5+/− T-cells

Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gα i2 and Gα i3 in thymocyte and T cell function, we developed several mouse models. Gα i2 deficiency in hematopoietic progenitors led to a small thymus, a double...

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Bibliographic Details
Published in:Scientific reports 2017-06, Vol.7 (1), p.4156-14, Article 4156
Main Authors: Hwang, Il-Young, Harrison, Kathleen, Park, Chung, Kehrl, John H.
Format: Article
Language:English
Subjects:
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Animal models
CD4 antigen
CD8 antigen
CXCR5 protein
Hemopoiesis
Humanities and Social Sciences
Immunological memory
Lymphocytes
Lymphocytes T
Memory cells
multidisciplinary
PD-1 protein
Proteins
Rodents
Science
Science (multidisciplinary)
Spleen
Thymocytes
Thymus
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Summary:Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gα i2 and Gα i3 in thymocyte and T cell function, we developed several mouse models. Gα i2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus. In both models an abnormal distribution of memory and naïve CD4 T cells occurred, and peripheral CD4 and CD8 T cells had reduced chemoattractant responses. The loss of Gα i3 had no discernable impact, however the lack of both G-proteins commencing at the DP stage caused a severe T cell phenotype. These mice lacked a thymic medullary region, exhibited thymocyte retention, had a peripheral T cell deficiency, and lacked T cell chemoattractant responses. Yet a noteworthy population of CD4 + PD-1 + CXCR5 +/− cells resided in the spleen of these mice likely due to a loss of regulatory T cell function. Our results delineate a role for Gα i2 in early thymocyte development and for Gα i2/3 in multiple aspects of T cell biology.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-04537-4