{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD5L (also known as AIM) is a secreted glycoprotein belonging to the scavenger receptor cysteine‐rich superfamily that is predominantly expressed by macrophages in lymphoid and inflamed tissues and under the control of nuclear receptors such as LXR. Its multifaceted functions include the modulation of immune cell activation and lipid metabolism. For example, CD5L plays a critical role in T‐helper 17 cell biology by skewing non‐pathogenic versus pathogenic cell states through the regulation of intracellular lipid composition, restricting cholesterol biosynthesis, and thereby influencing the availability of ligands for the master transcription factor RORγt."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In macrophages, CD5L is involved in promoting an anti‐inflammatory cytokine profile via the activation of phosphatidylinositol 3-kinase and autophagy pathways through its interaction with the cell-surface receptor CD36; this leads to suppression of proinflammatory mediators such as TNF and IL-1β and a concomitant increase in IL-10 production"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, by acting as a pattern recognition receptor, CD5L binds conserved microbial components from bacterial and fungal sources, thereby contributing to innate host defense. Its regulatory influence extends to lipid handling in macrophages as well; CD5L facilitates the uptake of oxidized lipoproteins via CD36, promoting foam cell formation and influencing the development of atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the cancer context, elevated levels of CD5L have been associated with hepatocellular carcinoma, where it enhances cancer cell proliferation and confers resistance to apoptosis through interaction with molecular chaperones such as HSPA5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, altered circulating CD5L levels have been linked to inflammatory disorders—for instance, increased plasma CD5L in atopic dermatitis may affect eosinophil survival and proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and in Staphylococcus aureus pneumonia elevated CD5L appears to exacerbate inflammatory pathology, with antibody-mediated neutralization conferring protection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Interestingly, extracellularly CD5L can also associate with other secreted proteins—for example, it forms heterologous complexes with the p40 monomer, acting as an adaptor that may generate novel composite cytokine-like molecules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, CD5L contributes to host defense against Mycobacterium tuberculosis by enhancing macrophage bactericidal activity, a process linked to the regulation of intracellular signaling and autophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these observations highlight CD5L as a key integrator of lipid metabolism, autophagy, and immune modulation with implications spanning autoimmunity, infection, metabolic disorders, and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chao Wang, Nir Yosef, Jellert Gaublomme, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.10.068"}], "href": "https://doi.org/10.1016/j.cell.2015.10.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26607793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26607793"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lucía Sanjurjo, Núria Amézaga, Gemma Aran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2015.1017183"}], "href": "https://doi.org/10.1080/15548627.2015.1017183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25713983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25713983"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lucía Sanjurjo, Gemma Aran, Érica Téllez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.00480"}], "href": "https://doi.org/10.3389/fimmu.2018.00480"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29593730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29593730"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Núria Amézaga, Lucía Sanjurjo, Josep Julve, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.1212660"}], "href": "https://doi.org/10.1189/jlb.1212660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24295828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24295828"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gemma Aran, Lucía Sanjurjo, Cristina Bárcena, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201700941RR"}], "href": "https://doi.org/10.1096/fj.201700941RR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29465313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29465313"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Won Kon Kim, Hyang Ran Hwang, Do Hyung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycoproteomic analysis of plasma from patients with atopic dermatitis: CD5L and ApoE as potential biomarkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3858/emm.2008.40.6.677"}], "href": "https://doi.org/10.3858/emm.2008.40.6.677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19116453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19116453"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xun Gao, Xingxing Yan, Qun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD5L contributes to the pathogenesis of methicillin-resistant Staphylococcus aureus-induced pneumonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2019.03.057"}], "href": "https://doi.org/10.1016/j.intimp.2019.03.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30959370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30959370"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kaveh Abdi, Nevil J Singh, Eric Spooner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Free IL-12p40 monomer is a polyfunctional adaptor for generating novel IL-12-like heterodimers extracellularly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1400159"}], "href": "https://doi.org/10.4049/jimmunol.1400159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24821971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24821971"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lucía Sanjurjo, Núria Amézaga, Cristina Vilaplana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The scavenger protein apoptosis inhibitor of macrophages (AIM) potentiates the antimicrobial response against Mycobacterium tuberculosis by enhancing autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0079670"}], "href": "https://doi.org/10.1371/journal.pone.0079670"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24223991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24223991"}]}]}]}