LECT2 : A pleiotropic and promising hepatokine, from bench to bedside

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.

Section: The Molecular Structure and Tissue Distribution Of Lect2mentioning

confidence: 99%

“…Besides its soluble functioning as a cytokine or hepatokine, LECT2 also exists in the form of amyloidosis (aLECT2) and is involved in renal and hepatic amyloid lesions (16)(17)(18). aLECT2 has been found to deposit in vessels, interstitial, and glomeruli of renal biopsies (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

Liu²,

Li³

et al. 2023

“…LECT2 is a hormone-like protein initially recognized as a neutrophil chemokine ( 160 ). Secreted by hepatocytes into the bloodstream, LECT2 serves as a multifunctional factor involved in numerous pathological conditions ( 161 ). In the bone marrow, LECT2 is capable of stimulating macrophages and modulating TNF expression through interaction with CD209a, consequently influencing HSC homeostasis ( 107 ).…”

Section: Immunomodulation Of the Livermentioning

confidence: 99%

Interorgan communication with the liver: novel mechanisms and therapeutic targets

Zhao,

Zhang,

et al. 2023

The liver is a multifunctional organ that plays crucial roles in numerous physiological processes, such as production of bile and proteins for blood plasma, regulation of blood levels of amino acids, processing of hemoglobin, clearance of metabolic waste, maintenance of glucose, etc. Therefore, the liver is essential for the homeostasis of organisms. With the development of research on the liver, there is growing concern about its effect on immune cells of innate and adaptive immunity. For example, the liver regulates the proliferation, differentiation, and effector functions of immune cells through various secreted proteins (also known as “hepatokines”). As a result, the liver is identified as an important regulator of the immune system. Furthermore, many diseases resulting from immune disorders are thought to be related to the dysfunction of the liver, including systemic lupus erythematosus, multiple sclerosis, and heart failure. Thus, the liver plays a role in remote immune regulation and is intricately linked with systemic immunity. This review provides a comprehensive overview of the liver remote regulation of the body’s innate and adaptive immunity regarding to main areas: immune-related molecules secreted by the liver and the liver-resident cells. Additionally, we assessed the influence of the liver on various facets of systemic immune-related diseases, offering insights into the clinical application of target therapies for liver immune regulation, as well as future developmental trends.

“…LECT2 primarily produces by hepatocytes, released into the bloodstream (8). It is widely distributed in the liver, kidneys, intestines, skin, and brain (9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Global research trends and hotspots for leukocyte cell-derived chemotaxin-2 from the past to 2023: a combined bibliometric review

Liu,

Wang,

Yeerlan

et al. 2024

Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in inflammatory response, immune regulation, disease occurrence and development. However, bibliometric study on LECT2 is lacking. In order to comprehend the function and operation of LECT2 in human illnesses, we examined pertinent studies on LECT2 investigation in the Web of Science database, followed by utilizing CiteSpace, VOSview, and Scimago Graphica for assessing the yearly quantity of papers, countries/regions involved, establishments, authors, publications, citations, and key terms. Then we summarized the current research hotspots in this field. Our study found that the literature related to LECT2 has a fluctuating upward trend. “Angiogenesis”, “ALECT2”, “diagnosis”, and “biliary atresia” are the current investigative frontiers. Our findings indicated that liver diseases (e.g. liver fibrosis and hepatic cell carcinoma), systemic inflammatory disease, and amyloidosis are the current research focus of LECT2. The current LECT2 research outcomes are not exceptional. We hope to promote the scientific research of LECT2 and exploit its potential for clinical diagnosis and treatment of related diseases through a comprehensive bibliometric review.