Science Bite (3 min Oral Presentation) Lorne Infection and Immunity 2019

New roles for myb in mature granulocytes (#77)

Kirsten Fairfax 1 , Jessica Bolden 1 , Erin Lucas 1 , Carolyn de Graaf 1 , Paul Giacomin 2 , Roger Pocock 3 , Douglas Hilton 1
  1. The Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. James Cook University, Cairns, Qld
  3. Monash Biomedicine Discovery Institute, Monash, Vic, Australia

Myb is an important transcription factor involved in both erythroid and lymphocyte lineage specification, and is well known for its role in the development of blood1. Myb is expressed highly in progenitor cells and is critical for the regulation of a suite of genes responsible for the proliferation, differentiation and survival of haematopoietic progenitor cells2. However, Myb is also expressed in some mature haematopoietic lineages, and strikingly so in eosinophils, a cell type that does not proliferate extensively.  We set out to examine the role of Myb in eosinophil development. We created Mybfl/fl.Epxcremice that lack Myb specifically in eosinophils. These Mybfl/fl.Epxcremice displayed eosinophils with substantially lower side scatter, a measure of granularity. RNAseq data suggests these eosinophils have reduced expression of a number of genes important for eosinophil function, and ELISAs for eosinophil peroxidase confirm this at the protein level. The eosinophils from MybPlt4/Plt4hypomorphic mice similarly have reduced side scatter, they resemble eosinophils by cytospin and TEM, however, these eosinophils show a reduction in the number of crystalloid granules. Thus, these cells resemble something that may be considered an immature eosinophil. In vitro killing experiments and in vivo challenge experiments suggest these eosinophils develop and recruit normally up to a certain stage, but their anti-helminthic killing function both in vitro and in vivo is impaired.

  1. 1 Emambokus N, Vegiopoulus A, Harman B, Jenkinson E, Andreson G, Frampton J. Progression through key stages of hemopoiesis is dependent on distinct threshold levels of c-Myb. EMBO J. 2003: 22: 4478-4488.
  2. 2 Zhao L, Glazov E, Pattabiraman D, Al-Owaidi F, Zhang P, Brown M, Leo M and Gonda T. Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb. NAR 2011 Jun; 39(11):4664-4679.