4.5 Article

IL-7 production in murine lymphatic endothelial cells and induction in the setting of peripheral lymphopenia

Journal

INTERNATIONAL IMMUNOLOGY
Volume 25, Issue 8, Pages 471-483

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxt012

Keywords

endothelium; HIV; interleukin-7; lymphatic; lymph node; lymphopenia; myeloid; stromal

Categories

Funding

  1. National Institutes of Health [DPI OD00329, R37 AI40312, U01AI43864, 5K23AI081540]
  2. Harvey V. Berneking Living Trust
  3. National Institutes of Health Medical Scientist Training Program [GM007618]
  4. National Institutes of Health Director's Pioneer Award Program, part of the National Institutes of Health Roadmap for Medical Research [DPI OD00329]

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IL-7 is a required factor for T-cell homeostasis. Because of low expression levels and poor reagent availability, the cellular sources of IL-7 have proven challenging to characterize. In this study, we describe a reporter mouse in which enhanced GFP is expressed from the endogenous Il7 locus. We show that IL-7 is produced by lymphatic endothelial cells (LECs) distributed throughout the systemic lymphatic vasculature as well as by fibroblastic reticular cells, and that phosphorylation of STAT5 in lymphocytes is higher in lymphatics than in blood. Furthermore, in nodes depleted of lymphocytes, Il7 transcription is increased in stromal but not in myeloid subsets. These data support recent findings that lymphocyte homeostasis is influenced by access to secondary lymphoid organs and point to LECs as an important in vivo source of IL-7, bathing trafficking immune cells under both resting and lymphopenic conditions.

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