Maria Guillamot

Abstract Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions systemic responses are poorly understood. Here, we leveraged a highly compartmentalized model of skin inflammation and identified a surprising type I interferon (IFN)-mediated activation of hematopoietic stem/progenitor cells (HSPCs) that results in profound changes to systemic host responses.

Ågerstam H. Karlsson C. Hansen N. Sandén C. Askmyr M. von Palffy S. Högberg C. Rissler M. Wunderlich M. Juliusson G. et al. Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia. Proc. Natl. Acad. Sci. USA. 2015; 112: 10786-10791 Alexandrov L.B. Nik-Zainal S. Wedge D.C. Aparicio S.A. Behjati S. Biankin A.V. Bignell G.R. Bolli N. Borg A. Børresen-Dale A.L. et al. Signatures of mutational processes in human cancer. Nature. 2013; 500: 415-421 Aran D.

Abstract The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown.