Figure 2.

A speculative model of TIM3-GAL9 axis in chronic kidney inflammation triggered by bacterial infection. (A) In acute stage of infection, bacterial antigens are presented to T cells by macrophage (MP) or antigen-presenting cell (APC). Upon activation, the primed T cells proliferate with TIM3 induction. With the synergic action of MHC II-antigen-TCR complex, TIM3-GAL9 interaction promotes the effector T cells that secrete abundant pro-inflammatory cytokines, like TNFα and IFNγ, to enhance bactericidal capacities of the phagocytes. Likewise, these paracrine cytokines induce activation of peripheral effector cells and amplify the systemic inflammatory response. (B) Upon pathogens clearance, the MHC-antigen-TCR complex unravels. TIM3-GAL9 axis, in turn, exerts an inhibitory action on T cells by induction of regulatory cytokines (like IL10 and TGFβ). In this context, TIM3-GAL9 interaction facilitates the resolution of tissue inflammation by induction of T cells apoptosis and transition of memory immune cells. (C) In the case of chronic/refractory infection, the immune system fails to eliminate the intracellular bacteria. The synergy of the MHC-antigen-TCR complex with the TIM3-GAL9 axis persistently stimulates the activation of peripheral immune cells, which are attracted into the involved kidneys of CKD by diseased renal microenvironment and participate in progressive kidney inflammation.