Figure 7

Proposed mechanism of origin and differentiation of CCR9⁺Mφs in Con A induced acute liver inflammation.

Following Con A administration, CCR9 negative monocytes derived from MDP-like progenitors egress from BM depending on CCR2. Then, blood circulating monocytes from BM infiltrate into the injured liver by chemokines/cytokines/attachment dependent migration. Once monocytes infiltrate into the injured liver through sinusoidal lumen, monocytes interact with activated HSCs (e.g. retinoic acid from activated HSCs) and differentiate into CCR9⁺Mφs with a potential of proliferation as well as antigen presentation to T cells. Thus, CCR9⁺Mφs are originated from BM independently on whole heterogeneous hepatic resident Mφs (including Kupffer cells and also resident perivascular Mφs), and differentiated in injured liver with local proliferation to promote acute liver inflammation.