Journal Article

High levels of IL-7 cause dysregulation of thymocyte development

Nahed El-Kassar, Francis A. Flomerfelt, Baishakhi Choudhury, Lee A. Hugar, Kevin S. Chua, Veena Kapoor, Philip J. Lucas and Ronald E. Gress

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 10, pages 661-671
Published in print October 2012 |
Published online August 2012 | | DOI: http://dx.doi.org/10.1093/intimm/dxs067

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IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocyte–stromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus. Our data reveal that high levels of IL-7 negate Notch-1 function in thymocytes found in IL-7 transgenic mice and in co-culture with OP9-DL1 cells. While high levels of IL-7R are present on thymocytes, increased suppressor of cytokine signaling-1 expression blunts IL-7 downstream signaling, resulting in hypo-phosphorylation of proteins in the PI3K-Akt pathway. Consequently, GSK3β remains active and inhibits Notch-1 signaling as observed by decreased Hes-1 and Deltex expression in thymic progenitors. This is the first demonstration that high levels of IL-7 antagonize Notch-1 signaling and suggest that IL-7 may affect T- versus B-lineage choice in the thymus.

Keywords: CD127; IL-7; IL-7R; Notch-1; thymus

Journal Article.  7494 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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