TLR10 is the only member of the TLR family that does not yet have a clearly defined function or ligand. Data from the literature are contradictory, as some studies link it to the induction of inflammation, while others show that TLR10 can inhibit inflammatory processes under certain conditions. Using the A549 cell line, we created models to study the immunomodulatory role of TLR10 in lung cells. With CRISPR/(d)Cas9 technology, we developed cellular models with overexpressed and down-regulated TLR10, enabling us to examine its impact on inflammatory responses in immune-stimulated cells. We found that TLR10 is a regulatory receptor of innate immunity, with its influence on TLR signaling pathways dependent on its expression level. Over-expression of TLR10 in A549 cells led to a reduction in proinflammatory factors, while its absence resulted in elevated inflammatory mediator expression. TLR10 modulates inflammation in the presence of TLR ligands, such as dsRNA, LPS, and Pam3Cys, as well as SARS-CoV-2 proteins S and N, particularly in the early stages of infection. We also confirmed that it suppresses proinflammatory cytokines (IL1β, TNFα, IL8) while enhancing the antiinflammatory cytokine IL10. The addition of 1,25-dihydroxyvitamin D increases TLR10 expression. In diseases where immune response regulation is crucial, modulating TLR10 expression could influence disease progression and reduce tissue damage.
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