Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset.

Blood
Jan HülsdünkerRobert Zeiser

Abstract

Conditioning-induced damage of the intestinal tract plays a critical role during the onset of acute graft-versus-host disease (GVHD). Therapeutic interference with these early events of GVHD is difficult, and currently used immunosuppressive drugs mainly target donor T cells. However, not donor T cells but neutrophils reach the sites of tissue injury first, and therefore could be a potential target for GVHD prevention. A detailed analysis of neutrophil fate during acute GVHD and the effect on T cells is difficult because of the short lifespan of this cell type. By using a novel photoconverter reporter system, we show that neutrophils that had been photoconverted in the ileum postconditioning later migrated to mesenteric lymph nodes (mLN). This neutrophil migration was dependent on the intestinal microflora. In the mLN, neutrophils colocalized with T cells and presented antigen on major histocompatibility complex (MHC)-II, thereby affecting T cell expansion. Pharmacological JAK1/JAK2 inhibition reduced neutrophil influx into the mLN and MHC-II expression, thereby interfering with an early event in acute GVHD pathogenesis. In agreement with this finding, neutrophil depletion reduced acute GVHD. We conclude that neutrophils are at...Continue Reading

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Citations

Jul 26, 2018·Journal of Leukocyte Biology·Carolyne K Smith, Giorgio Trinchieri
Sep 28, 2018·Immunology·Sara CostaPatrizia Scapini
Nov 20, 2018·Current Opinion in Hematology·David C Dale
Sep 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jan HülsdünkerRobert Zeiser
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Sep 6, 2021·Blood·Robert Zeiser, Takanori Teshima

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