Data from: Aryl hydrocarbon receptor activation alters emergency hematopoiesis during influenza A virus infection

Hematopoietic stem and progenitor cells (HSPCs) produce all cells of the
blood and immune system in a process known as hematopoiesis. During
infection, there is an increased demand for immune cells, which causes
HSPCs to rapidly and transiently modify cellular output, a response
described as emergency hematopoiesis. Small molecules from the host
environment may contribute to signals that regulate emergency
hematopoiesis, providing a means to influence important processes during
infection. Environmental exposures have long been associated with altered
immune responses in the human population and experimental studies.
Specifically, chemicals that bind the aryl hydrocarbon receptor (AHR)
modulate immune responses in a broad range of contexts, including during
viral infection. Separate studies have shown that AHR signaling also
influences steady-state hematopoiesis. Using two different AHR ligands,
2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and
2-(1H-indol-3-ylcarbonyl)-4-thiazole-carboxylic acid methyl ester (ITE),
we characterized the impact of AHR activation on the proportion of HSPC
and lineage-committed progenitor cells over the course of an influenza A
virus infection in mice. AHR activation via these two ligands had a
distinct impact on HSPCs, yet affected monocytes in the blood and lung
similarly. For example, AHR activation with TCDD, but not ITE, increased
myeloid-biasing among HSPC. However, the frequency of monocytes in the
lung was reduced by either TCDD or ITE treatment. Using Vav1CreAhrfxfx
mice, we showed that these effects depend on AHR expression in
hematopoietic cells. Collectively, these findings highlight the
differential effects of AHR ligands and their role in regulating emergency
hematopoiesis in response to a common respiratory pathogen.