Myeloid cells accumulate in the intestine in mouse models of colitis, but how this aberrant increase occurs and what part it plays in the disease are unclear. Griseri et al. now report that altered hematopoiesis is responsible for the increased myeloid cell number and is a pathogenic in colitis (Immunity doi:10.1016/j.immuni.2012.08.025).

In colitic mice, the researchers found increased proliferation of hematopoietic stem cells (HSCs) and skewing of common myeloerythroid progenitors toward granulocyte-monocyte progenitors (GMPs) in the bone marrow and spleen. Highly proliferative GMPs were also found in the colon, and the authors propose that these changes in hematopoietic subsets account for the increased numbers of neutrophils and inflammatory monocytes seen in the spleen and colon of mice with colitis. Although granulocyte colony–stimulating factor (G-CSF) and granulocyte-macrophage colony–stimulating factor (GM-CSF) (key cytokines in granulocyte and monocyte differentiation) did not induce accumulation of GMPs in the mouse colon, GM-CSF blockade prevented the increase in GMPs and reduced the severity of colitis. Moreover, transfer of GMPs from colitic mice enhanced disease in secondary recipients.

The researchers further showed that interferon-γ (IFN-γ), which is produced by colitogenic T cells and can induce HSC proliferation, was responsible for the increase in HSCs in bone marrow in their model of colitis. The authors describe a model in which interleukin-23 induces IFN-γ and GM-CSF production by T and other cells, which trigger, respectively, HSC proliferation and increased GMP recruitment and proliferation and differentiation in the colon, thereby contributing to intestinal inflammation. Their findings uncover a pathogenic role for hematopoietic stem and progenitor cells in experimental colitis.