In vivo depletion and genetic targeting of mouse intestinal CX3CR1+ mononuclear phagocytes

Mononuclear phagocytes (MPs) are an essential component of the intestinal immune system. They are comprised of a few dendritic cell and macrophage subsets, all with the common ability to sample extracellular milieu and to discriminate between dangerous and innocuous signals. Despite the commonality, each MP subset acquires distinct developmental pathways and unique functions, likely to fulfill needs of the tissue in which they reside. Some MP subsets develop from monocytes and are distinguished by their expression of CX3C-chemokine receptor 1 (CX3CR1). This manuscript summarizes our expertise in vivo targeting of intestinal CX3CR1+ MP subsets. The described tools might be useful for studies of CX3CR1+ MP function in various murine experimental models, particularly under non-inflammatory conditions. Diversity of intestinal MP subsets at steady state. CD11chi CD103+CD11b− DCs (green), CD103+CD11b+ DCs (blue) and CD103−CD11b+ MPs (red) are distributed throughout the mucosa. CD103+CD11b+ DCs and CD103−CD11b+ MPs can be associated with the intestinal epithelium (yellow), whereas CD103+CD11b− DCs are found in the deeper mucosa and are likely localized to the isolated lymphoid follicles (ILFs) (Bogunovic et al., 2009; Koscso et al., 2015). CD103−CD11b+ MPs are further divided into CX3CR1hi Mϕs that are tissue-resident, and CX3CR1int MPs that migrate to the MLNs similar to CD103+CD11b− and CD103+CD11b+ DCs. CD11clo CD103−CD11b+ Mϕs are distributed in the muscularis externa along the myenteric plexus formed by enteric neurons (black). [Display omitted] •Intestinal CX3CR1+ mononuclear phagocyte (MP) subsets are characterized by the common expression of CSF1R and LYZ2.•In vivo blockade of CSF1R with the monoclonal antibody selectively depletes intestinal CX3CR1+ MP subsets.•Constitutive cre expression under Lyz2 promoter targets mainly CX3CR1+ MP subsets in the gut and mesenteric lymph nodes.•Tamoxifen-inducible cre expression under Csf1r promoter targets all intestinal MP subsets including CX3CR1+ MPs.