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. 2022 Jun 28;10:922041. doi: 10.3389/fcell.2022.922041

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Copyright © 2022 Wang and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Interaction of immune cells in the liver revealed by IVM. Multiple immune cells interact with each other in both physiological and pathological conditions in the liver. Many cells in the liver can act as antigen-presenting cells to interact with T cells. KCs express both MHCⅠ and MHCⅡ and many costimulatory molecules and present antigens to naive CD4⁺ or CD8⁺ T cells for their activation and priming. The antigen presentation to CD8⁺ T cells by KCs induces full differentiation to effector CD8⁺ T cells, while the antigen presentation to CD4⁺ T cells by KCs induces differentiation into Treg. Hepatocytes also present antigens to CD8⁺ T cells, but this leads to exhaustion of CD8⁺ T cells. KCs activate iNKT cells via CD1d. Interaction among KCs, neutrophils, and platelets provides defense against bacteria invasion, and neutrophil–platelet interaction is necessary for NET formation. In addition, KCs also recognize apoptotic cells and interact with senescent and apoptotic erythrocytes, platelets, and neutrophils for the clearance of dying immune cells.