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Immune System Imaging
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Michael J. Hickey, M. Ursula Norman
Early intravital microscopy studies examined the mechanisms whereby T cells entered the lymph node from the bloodstream via interactions in HEV. Endothelial cells in HEV express an adhesion molecule signature that facilitates interactions of circulating naïve lymphocytes, enabling these cells to enter the lymph node via a sequence of interactions, culminating in transmigration. Using epifluorescence intravital microscopy to visualize the lymph node, Von Andrian and Warnock (von Andrian, 1996; Warnock et al., 1998) demonstrated that lymphocytes rolled and adhered in paracortical HEV, with lymphocyte rolling being dependent on L-selectin and adhesion on LFA-1. Subsequent experiments revealed a role for the CCR7 ligand CCL21 in mediating arrest of rolling lymphocytes, demonstrating the importance of this pathway in delivery of naïve lymphocytes into the lymph node (Stein et al., 2000).
Biomimetic Microsystems for Blood and Lymphatic Vascular Research
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Tumor immunotherapies have been emerging, and a few strategies are already used in the clinics for blood cancers. Tumor lymphatics largely influence tumor immunity. Lymphatics-induced immune modification and tumor immune tolerance have been reported (Swartz and Lund 2012). Although the lymph nodes are abundant with T/B lymphocytes and tumor antigen-specific immune reactions normally occur in the lymph nodes, tumor cells invaded lymph nodes even establish and maintain tumor growing niche without normal lymph node function against tumor cells. This suggests that tumor cells might modify the lymph node environment, thus impairing host immunity. One proposed mechanism is that CCL21 expressed by lymphatics recruits CCR7-positive naive T cells into the lymph nodes and tumor stroma where they are educated to be less immune reactive. Similarly, CCR7-positive DCs are maintained in their immature state in the primary tumors and the tumor draining lymph nodes. Further, the immature DCs promote tumor-associated regulatory T cell activity to suppress cytotoxic T lymphocytes. TGFβ secreted in tumors also inhibits natural killer cell functions. TGFβ promotes tumor-associated regulatory T lymphocytes, causing tumor immune tolerance (Swartz and Lund 2012). Further tumor lymphatics expressed programmed death-ligand 1 (PD-L1) that can bind to PD-1 on T lymphocytes and induce an inhibitory signal that reduces proliferation of antigen-specific T lymphocytes (Dieterich et al. 2017). While several studies have described immunosuppressive roles of tumor lymphatics, one recent study revealed that tumor lymphatics can serve as a route of cytotoxic T-cell entrance to the tumor, synergistically boosting anti-tumor immunity (Fankhauser et al. 2017). Lymphatics-mediated tumor immunity is still controversial and needs further investigations.
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
Skin irritation is produced by damage to epidermal cells via direct contact with the chemical substance. Acute disruption of the epidermal barrier results in the release of a preformed pool of cytokines including IL-1α, thus leading to an immediate initial irritant reaction and subsequently induction of barrier repair mechanisms (Kim et al. 2019, 2018). For example, in repeated exposure to sodium lauryl sulfate (SLS), an elevated IL-1 receptor antagonist (IL-1 RA)/ IL-1α ratio was observed, primary to arise in IL-1α RA. Fluhr et al. (2008) proposed that IL1α is derived from damaged keratinocytes during the interaction between irritant and epidermal barrier. IL1α serves as a signal to the release of chemokines CCL20 and CXCL8 that attract a variety of cells including T cells, B cells, neutrophils and immature DCs) mediating the immune response in the skin and resulting in a proinflammatory effect (Fluhr et al. 2008). In addition, irritants – such as SLS, toluene, trichloroacetic acid, sodium hypochlorite, salicylic acid, sodium hydroxide, glycolic acid and benzalkonium chloride – induce CCL21 chemokine up-regulation by dermal lymphatic endothelial cells. CCL21 may enhance the steady-state emigration of CCR7+ LC (Eberhard et al. 2004). Skin sensitization- and irritation-derived mechanisms are generally not fully understood.