Heterodimers of Toll-like receptors (TLR) in the pathogenesis of systemic inflammation (Review article)

In recent decades, fundamental discoveries in biology and medicine have allowed for a new look at the main pathophysiological mechanisms of systemic inflammation formation in many pathological conditions, both infectious and non-infectious etiology. The TLRs family acts as a bridge linking innate and acquired immunity, mediates the initial innate immune responses, and is necessary for the development of an adaptive immune response.

The aim. To draw the attention of specialists to the role of TLR heterodimers in the development of infl           and to show that it can become new targets in drug development.

Materialsandmethods. Writingthereview, domesticandforeignliteratureofthe Google, PubMed and eLibrary systems (1998-2024) was analyzed.

The results and discussion. TLRs recognize a wide range of different related ligands with their extracellular leucine-rich repeating domains (LRRs), triggering signal transmission inside the target cell through sequential activation of cytoplasmic adapter molecules, kinases, and nuclear transcription factor. The literature data on TLRs heterodimers, which include TLR1, TLR2, TLR4, TLR6, and TLR10, are presented. The formation and composition of heterodimers are determined by the structure of the pathogen. Functionally, heterodimers provide an optimal cell response, including the synthesis of effector molecules: proand anti-inflammatory cytokines, chemokines, and inflammatory mediators. Co-receptors, in particular CD14 / CD36, are involved in binding TLR heterodimers to a specific ligand.

Conclusion. An analysis of the literature data had shown the important role of TLR heterodimers and the signaling pathways activated by them in the pathogenesis of many diseases. Understanding these molecular mechanisms could contribute to the development of a more effective treatment strategy. Of particular interest is the creation of new targeted drugs that affect the Toll-receptor system, which is a new direction in the treatment of allergies, autoimmune pathology, and chronic inflammation.

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