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Braf V600E expression in resident macrophage progenitors leads to clonal expansion of ERK-activated microglia, which causes synaptic and neuronal loss in the brain and results in lethal neurodegenerative disease in adult mice.
The size of immune-cell populations needs to be tightly regulated. Shinohara and colleagues demonstrate that intracellular and secreted osteopontin control the contraction and expansion of myeloid and lymphoid populations differently under infectious and autoimmune conditions.
The ability to expand and contract populations of myeloid and lymphoid cells during emergency hematopoiesis helps shape the immune response. The expression of intracellular and soluble forms of osteopontin regulates apoptosis thresholds differently in myeloid cells and lymphoid cells to counter infection.
Increased expression of the ubiquitin ligase TRAF6 in hematopoietic stem cells promotes activity of the GTP-binding protein Cdc42 and consequent diminished function of hematopoietic stem cells by ubiquitination of the RNA-binding protein hnRNP-A1, which leads to an inability to properly process pre-mRNA encoding Cdc42-inhibitory GTPase-activating proteins.