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The micro-environment of the lymphatic organs can help the body maintain healthy immune function through structural and molecular support. Although studies in mice have found that fibroblastic cell mesh cells (FRCs) in mice create a necessary T-cell support structure in the lymph nodes, little research has been done on the function of human FRCs.
recently from the University of Birmingham, Genentech and other institutions found that human FRCs use four mechanisms simultaneously during exo-T cell activation to create a regulatory immune checkpoint micro-environment. FRCs, the source of human tonsils and lymph nodes, can limit the activation of initial T-cells and inactive T-cells, allowing them to differentiate away from the central memory T-cell ideotype.
FRCs unilaterally create an immunosuppressive environment through pyridoxine-2, 3-dooxygenase, adenosine 2A subject, prostatin E2, and transformation growth factor subjects without the need for feedback from T cells. Since each signaling path can be inhibited by drugs, cocktail therapy targeting inhibitors for these four mechanisms can completely reverse the immunosuppressive effects of FRCs.
T-cells are not permanently inhibited by FRCs, and experiments using the chimic antigen-inhibitor T-cell therapy have shown that these T-cells still maintain effect function without FRCs. Since mice were not suitable for studying the problem, the researchers developed an in-place experiment based on human tissue. The researchers found that using standard methods to stimulate T cells in fresh tonsil slices did not multiply, but only under the action of the above inhibitors.
Overall, the researchers found that FRCs in the body regulate the mechanism by which T cells in the outer lymphatic organ function in the external lymphatic organ through four signaling paths, and that although these T-cells are inhibited, they can still be used for CAR T therapy. The study showed that drug-targeted FRCs to suppress these four signaling path paths (used alone or in a joint way) can enhance the initial T-cell response to infection and cancer. (Bio Valley)