The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

Leukocyte cell-derived chemotaxin-2 (LECT2, also named ChM-II), initially identified as a chemokine mediating neutrophil migration, is a multifunctional secreted factor involved in diverse physiological and pathological processes. The high sequence similarity of LECT2 among different vertebrates makes it possible to explore its functions by using comparative biology. LECT2 is associated with many immune processes and immune-related diseases via its binding to cell surface receptors such as CD209a, Tie1, and Met in various cell types. In addition, the misfolding LECT2 leads to the amyloidosis of several crucial tissues (kidney, liver, and lung, etc.) by inducing the formation of insoluble fibrils. However, the mechanisms of LECT2-mediated diverse immune pathogenic conditions in various tissues remain to be fully elucidated due to the functional and signaling heterogeneity. Here, we provide a comprehensive summary of the structure, the double-edged sword function, and the extensive signaling pathways of LECT2 in immune diseases, as well as the potential applications of LECT2 in therapeutic interventions in preclinical or clinical trials. This review provides an integrated perspective on the current understanding of how LECT2 is associated with immune diseases, with the aim of facilitating the development of drugs or probes against LECT2 for the theranostics of immune-related diseases.

Automated summary

Leukocyte cell-derived chemotaxin-2 (LECT2) is a multifunctional secreted factor involved in various physiological and pathological processes, including immune processes and immune-related diseases. It interacts with cell surface receptors such as CD209a, Tie1, and Met, and can lead to amyloidosis in important tissues. The mechanisms of LECT2-mediated immune pathogenic conditions in different tissues are still not fully understood due to functional and signaling heterogeneity. This review provides a comprehensive understanding of LECT2's structure, function, signaling pathways, and potential applications in theranostics of immune-related diseases.