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Fig. 4 | Arthritis Research & Therapy

Fig. 4

From: Senescence in osteoarthritis: from mechanism to potential treatment

Fig. 4

Interactions between NK cells and senescent cells. In response to DNA damage, MICA is selectively expressed on senescent cells rather than proliferative cells. MICA interacts with NKG2D and activates NK cells via ITAM. Activated NK cells produce and secrete granzyme B and perforin to kill senescent cells. Shedding MICA from the senescent cell membrane surface leads to NK cells off-target and senescent cell evasion. HLA-E is upregulated by the p38 pathway. HLA-E binds to NKG2A and inhibits NK cell activation via the ITIM on the NKG2A intracellular segment. CD155 exerts dual effects as its combination with DNAM-1 activates NK cells while its combination with CD94 or TIGHT inhibits NK cell activation. Shedding CD155 participates is involved in the evasion of senescent cells as its binding affinity to DNAM-1 is higher than that to TIGHT and CD94. The expression of MICA and CD155 is directly regulated by transcriptional factor E2F1. uPAR is specifically expressed on the senescent cell membrane surface, and CAR-T therapy targeting uPAR has been designed to eliminate senescence. DPP4 has been treated as a target of immunotherapy via ADCC. NKG2D, natural killer group 2, member D; HLA-E, human leukocyte antigen-E; IL-6, interleukin-6; CAR-T cell, chimeric antigen receptor T cell; uPAR, urokinase-type plasminogen activator receptor; ADCC, antibody-dependent cell-mediated cytotoxicity; DPP4, dipeptide peptidase 4; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based inhibitory motif

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