{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:45Z","timestamp":1786969725991,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>For many decades, the regulation of immune responses, namely, the maintenance of self-tolerance and the prevention of pro-inflammatory processes, was attributed to the suppressive function of T and\/or B regulatory cells. However, the field of immune regulation was recently expanded to include not only many membrane-bound regulatory molecules on immune cells but also the release of many soluble molecules playing a role in the modulation of immune responses. Soluble checkpoint molecules are the subject of many recent studies, in which they were reported to function as both regulatory and stimulatory molecules. They are involved in the pathogenesis of immune-mediated disorders, infections, and cancer, and are involved in balancing immune effector responses with regulatory reactions. Many of them have become relevant targets in treating these diseases. In this review, we chose to focus on those soluble molecules whose role is attributed to immune-mediated diseases, namely in modulating autoimmunity by enhancing mechanisms of self-tolerance and immunosuppressive signals. The understanding of these mechanisms might facilitate the development of future therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms27167319","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Complexity of Soluble Checkpoint Molecules in Modulating Immune-Mediated Diseases and Autoimmunity"],"prefix":"10.3390","volume":"27","author":[{"given":"Elias","family":"Toubi","sequence":"first","affiliation":[{"name":"Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raeda","family":"Mubariki","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel"},{"name":"The Proteomic Unit, Bnai-Zion Medical Center, Haifa 31048, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahava","family":"Vadasz","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel"},{"name":"The Proteomic Unit, Bnai-Zion Medical Center, Haifa 31048, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, C., Liu, Y., Li, S., Du, M., Zhu, K., and Li, H. (2026). Regulatory T cells in primary Sjogren disease: Regulatory mechanisms and therapeutic prospects. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1802660"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105049","DOI":"10.1016\/j.cellimm.2025.105049","article-title":"The discovery of regulatory T cells: A paradigm shift in immunology","volume":"419","author":"Fillatreau","year":"2026","journal-title":"Cell. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Catalan, D., Mansilla, M.A., Ferrier, A., Sato, L., Oleinika, K., Aguillon, J.C., and Aravena, O. (2021). Immunosuppressive mechanisms of regulatory B cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.611795"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12929-026-01228-z","article-title":"TGF-\u03b2 signaling mediates crosstalk between CD8+ T cells and CD39+ induced T reg cells in autoimmune inflammation","volume":"33","author":"Chen","year":"2026","journal-title":"J. Biomed. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, X., Ji, Q., Zhang, Y., Wei, W., Mo, Z., and Chen, T. (2026). Regulatory B cells: Heterogeneity, immunosuppressive networks, and contributions to autoimmune pathogenesis. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1808399"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Al-Atiyah, R., Verma, N.D., Tran, G.T., Hodgkinson, S., and Hall, B.M. (2026). Cytokines associated with activation of CD4+CD25+Foxp3+ T regulatory cells. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27042085"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Maksimova, A., Tyrinova, T., and Chernykh, E. (2026). TIM-3+ macrophages: Insights into their role in cancer and inflammation. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020840"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/cyto.b.22266","article-title":"CD200 expression in CD4+T-cells: Diagnostic implications across T-cell lymphomas","volume":"110","author":"Chiriac","year":"2026","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1093\/jimmun\/vkaf040","article-title":"ICOS+CD4+ T cells promote antitumor immunity through Akt\/STAT1\/T-be axis in MSS\/pMMR colorectal cancer","volume":"214","author":"Luo","year":"2025","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2022.03.013","article-title":"Binding of LAG3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity","volume":"55","author":"Maruhashi","year":"2022","journal-title":"Immunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1093\/jimmun\/vkaf120","article-title":"LAG3-MHCII interaction induces a tight cell-cell interface at the immunological synapse","volume":"214","author":"Wang","year":"2025","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jaut.2016.09.005","article-title":"Identification of tonsillar CD4+CD25-LAG3+ T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue","volume":"76","author":"Sumitomo","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6329","DOI":"10.1038\/ncomms7329","article-title":"TGF-\u03b23-expressing CD4+CD25-LAG-3+ regulatory T cells control humoral immune responses","volume":"19","author":"Okamura","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1084\/jem.20100466","article-title":"PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice","volume":"208","author":"Okazaki","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hashimoto-Tane, A., Bowman, E.P., Sakuma, M., Yoneda, N., Yugi, K., de Waal Malefyt, R., and Saito, T. (2024). Dissociation of LAG3 inhibitory cluster from TCR microcluster by immune checkpoint blockade. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1444424"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s00011-023-01742-y","article-title":"From bench to bedside: Targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases","volume":"72","author":"Zhou","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102283","DOI":"10.1016\/j.coi.2023.102283","article-title":"Immune checkpoint receptors in autoimmunity","volume":"80","author":"Burke","year":"2023","journal-title":"Curr. Opin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zong, Y., Deng, K., and Chong, W.P. (2024). Regulation of T reg cells by cytokine signaling and co-stimulatory molecules. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1387975"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Negrini, S., Nicola, S., Badiu, L., Quinternetto, A., Vitali, I., Sardo, L.L., and Brussino, L. (2026). The CTLA-4 pathway in human disease: Molecular mechanisms and therapeutic targeting. Genes, 17.","DOI":"10.3390\/genes17050574"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.jaci.2025.08.027","article-title":"Abatacept restores dysregulated transcriptomic and proteomic profile in disorders of CTLA-4","volume":"156","author":"Catak","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41586-022-05432-3","article-title":"T cells specific for a-myosin drive immunotherapy-related myocarditis","volume":"611","author":"Axelrod","year":"2022","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"507","DOI":"10.4049\/immunohorizons.2200049","article-title":"Preferential expansion of Foxp3+ T regulatory cells in CTLA-4-deficient and CTLA-4 haploinsuficient C57BL\/6 mice","volume":"6","author":"Stohl","year":"2022","journal-title":"Immunohorizons"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/25785826.2019.1660038","article-title":"Inhibitory B cell co-receptors and autoimmune diseases","volume":"42","author":"Tsubata","year":"2019","journal-title":"Immunol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"Keag097","DOI":"10.1093\/rheumatology\/keag097","article-title":"CD72 downregulation on DN2 B cells is associated with disease activity and resistance to rituximab in systemic lupus erythematosus","volume":"65","author":"Wangriatisak","year":"2026","journal-title":"Rheumatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.semarthrit.2013.11.010","article-title":"A regulatory role for CD72 expression on B cells in systemic lupus erythematosus","volume":"43","author":"Vadasz","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103245","DOI":"10.1016\/j.jaut.2024.103245","article-title":"CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes suppresses production of anti-ribosome autoantibody","volume":"146","author":"Akatsu","year":"2024","journal-title":"J. Autoimmun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pereira, J.A., Lanzar, Z., Clark, J.T., Hart, A.P., Douglas, B., Shallberg, L., O\u2019Dea, K., Christian, D.A., and Hunter, C.A. (2023). PDL1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.997376"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1007\/s00421-023-05251-y","article-title":"Intensity-and time-matched acute interval and continuous endurance exercise similarly induce an anti-inflammatory environment in recreationally active runners: Focus on PD-1 expression in Tregs and IL-6\/IL-10 axis","volume":"123","author":"Proschinger","year":"2023","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Memida, T., Cao, G., Abdolahinia, E.D., Ruiz, S., Huang, S., Hassantash, S., Shindo, S., Okamoto, M., Yamashita, S., and Nakamura, S. (2025). B10 promotes polarization and pro-resolving functions of bone marrow derived macrophages (BMDM) through PD-1 activation. Cells, 141.","DOI":"10.3390\/cells14120860"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E70006","DOI":"10.1002\/cti2.70006","article-title":"Characteristics of PD-1+CD4+ T cells in peripheral blood and synovium of rheumatoid arthritis patients","volume":"13","author":"Chen","year":"2024","journal-title":"Clin. Transl. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"152582","DOI":"10.1016\/j.semarthrit.2024.152582","article-title":"Immune checkpoint inhibitors and rheumatoid arthritis: All roads lead to PD-1?","volume":"70S","author":"Cappelli","year":"2025","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6249","DOI":"10.1007\/s12035-021-02495-7","article-title":"Role of the PD-1\/PD-L1 signaling in multiple sclerosis and experimental autoimmune encephalomyelitis: Recent insights and future directions","volume":"58","author":"Mi","year":"2021","journal-title":"Mil. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s11481-025-10206-5","article-title":"Unmasking a paradox: Roles of the PD-1\/PD-L1 axis in Alzheimer\u2019s disease-associated neuroinflammation","volume":"20","author":"Moadab","year":"2025","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"156136","DOI":"10.1016\/j.cyto.2023.156136","article-title":"Majoon chobchini reinstates PDL-1 expression and blocks dendritic cell-T helper 17 pathogenic axis in rheumatoid arthritis animal model","volume":"163","author":"Samarpita","year":"2023","journal-title":"Cytokine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-immunol-121824-071940","article-title":"Emerging roles of CD1 and lipids in human health and disease","volume":"44","author":"Rossjohn","year":"2026","journal-title":"Annu. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, Y., Li, C., Lu, Y., Zhuang, H., Gu, W., Liu, B., Liu, F., Sun, J., Yan, B., and Weng, D. (2017). IL-10-producing CD1dhiCD5+ regulatory B cells may play a critical role in modulating immune homeostasis in silicosis patients. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00110"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41467-018-02911-y","article-title":"CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells","volume":"9","author":"Oleinika","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/1756-185X.14691","article-title":"Role of CD19+ CD5+ CD1d+ Bregs in maintaining the Th17\/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis","volume":"26","author":"Zhu","year":"2023","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"578673","DOI":"10.1016\/j.jneuroim.2025.578673","article-title":"Therapeutic potential of S-nitrosoglutathione reductase inhibitor in B cell-driven experimental autoimmune encephalomyelitis","volume":"406","author":"Won","year":"2025","journal-title":"J. Neuroimmunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"115602","DOI":"10.1016\/j.celrep.2025.115602","article-title":"The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses","volume":"44","author":"He","year":"2025","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1177\/0961203320916517","article-title":"Serum levels of soluble programmed cell death protein 1 and soluble programmed cell death protein ligand 2 are increased in systemic lupus erythematosus and associated with the disease activity","volume":"29","author":"Hirahara","year":"2020","journal-title":"Lupus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12884","DOI":"10.1111\/sji.12884","article-title":"Serum levels of soluble programmed death -1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in systemic lupus erythematosus: Association with activity and severity","volume":"92","author":"Du","year":"2020","journal-title":"Scand. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.imlet.2020.09.001","article-title":"Abnormal membrane-bound and soluble programmed death ligand 2 (sPD-L2) expression in systemic lupus erythematosus is associated with disease activity","volume":"227","author":"Tong","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1177\/1076029614562952","article-title":"Soluble programmed death 1 (sPD-1) is decreased in patients with immune thrombocytopenia (ITP): Potential involvement of PD-1 pathway in ITP immunopathogenesis","volume":"22","author":"Atesoglu","year":"2016","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/21645515.2017.1342913","article-title":"Percentages of PD-1+CD4+ T cells and PD-L1+DCs are increased and sPD-1 level is elevated in patients with immune thrombocytopenia","volume":"14","author":"Wang","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/s13075-015-0859-z","article-title":"Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways","volume":"17","author":"Liu","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Okuyama, M., Mezawa, H., Kawai, T., and Urashima, M. (2019). Elevated soluble PD-L1 in pregnant women\u2019s serum suppresses the immune reaction. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00086"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Niu, M., Liu, Y., Yi, M., Jiao, D., and Wu, K. (2022). Biological characteristics and clinical significance of soluble PD-1\/PD-L1 and exosomal PD-L1 in cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.827921"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s13317-010-0011-7","article-title":"The soluble CTLA-4 receptor and its role in autoimmune diseases: An update","volume":"1","author":"Saverino","year":"2010","journal-title":"Autoimmun. Highlights"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"215763","DOI":"10.1155\/2014\/215763","article-title":"The soluble form of CTLA-4 from serum of patients with autoimmune diseases regulates T-cell responses","volume":"2014","author":"Simone","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.2337\/db11-0130","article-title":"The soluble CTLA-4 splice variant protects from type I diabetes and potentiates regulatory T-cell function","volume":"60","author":"Gerold","year":"2011","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mikus, M., Goldstajn, M.S., Brlecic, I., Dumancic, S., Lagana, A.S., Chiantera, V., Vuji\u0107, G., and \u0106ori\u0107, M. (2022). CTLA-4-linked autoimmunity in the pathogenesis of endometriosis and related infertility: A systematic review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810902"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13075-016-1075-1","article-title":"Immunoregulatory soluble CTLA-4 modifies effector T-cell responses in systemic lupus erythematosus","volume":"18","author":"Dahal","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1365-2249.2005.02815.x","article-title":"Increased expression of plasma and cell surface co-stimulatory molecules CTLA-4, CD28 and CD86 in adult patients with allergic asthma","volume":"141","author":"Wong","year":"2005","journal-title":"Clin. Exp. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"164","DOI":"10.5644\/ama2006-124.295","article-title":"Influence of innate immunity on immune tolerance","volume":"49","author":"Kucuksezer","year":"2020","journal-title":"Acta Med. Acad."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.4049\/jimmunol.164.10.5015","article-title":"Cutting edge: A soluble form of CTLA-4 in patients with autoimmune thyroid disease","volume":"164","author":"Oaks","year":"2000","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.clim.2007.01.003","article-title":"Soluble CTLA-4 in autoimmune thyroid diseases: Relationship with clinical status and possible role in the immune response dysregulation","volume":"123","author":"Saverino","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3109\/07357901003630934","article-title":"Circulating soluble CTLA-4 (sCTLA4) is elevated in patients with breast cancer","volume":"28","author":"Erfani","year":"2010","journal-title":"Cancer Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ymthe.2023.11.028","article-title":"Soluble CTLA-4 attenuates T cell activation and modulates anti-tumor immunity","volume":"32","author":"Kennedy","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.emboj.7601520","article-title":"Metalloproteases regulate T-cell proliferation and effector function via LAG3","volume":"26","author":"Li","year":"2007","journal-title":"EMBO J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.it.2003.10.001","article-title":"LAG-3: A regulator of T-cell and DC responses and its use in therapeutic vaccination","volume":"24","author":"Triebel","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13075-023-03073-z","article-title":"Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis","volume":"25","author":"Pedersen","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"ltab025","DOI":"10.1093\/immadv\/ltab025","article-title":"Seven mysteries of LAG3: A multi-faceted immune receptor of increasing complexity","volume":"2","author":"Burnell","year":"2022","journal-title":"Immunother. Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1002\/eji.200526090","article-title":"Expression of lymphocyte activation gene 3 (LAG3) on B cells is induced by T cells","volume":"35","author":"Kisielow","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2005.04.015","article-title":"A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors","volume":"235","author":"Triebel","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"874","DOI":"10.3324\/haematol.2016.148965","article-title":"Lymphocyte activation gene-3: A novel therapeutic target in chronic lymphocytic leukemia","volume":"102","author":"Shapiro","year":"2017","journal-title":"Haematologica"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"21319","DOI":"10.1038\/s41598-022-25466-x","article-title":"Soluble immune checkpoint molecules in patients with antineutrophil cytoplasmic antibody-associated vasculitis","volume":"12","author":"Pyo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"578308","DOI":"10.1016\/j.jneuroim.2024.578308","article-title":"Expression of lymphocyte activation gene-3 on CD4+ T cells is regulated by cytokine interleukin-18 in myasthenia gravis","volume":"388","author":"Tian","year":"2024","journal-title":"J. Neuroimmunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Xiong, X., Duan, Z., Zhou, H., Niu, L., Luo, Z., and Li, W. (2022). The relationship between soluble lymphocyte activation gene-3 and coronary artery disease. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.988582"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.4049\/jimmunol.1002373","article-title":"Invariant NKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner","volume":"186","author":"Yang","year":"2011","journal-title":"J. Immunol."},{"key":"ref_71","first-page":"481","article-title":"Low levels of soluble CD1d protein alters NKT cell function in patients with rheumatoid arthritis","volume":"24","author":"Segawa","year":"2009","journal-title":"Int. J. Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5304","DOI":"10.4049\/jimmunol.172.9.5304","article-title":"C1d1 displayed on cell size beads identifies and enriches an NK cell population negatively regulated by CD1d1","volume":"172","author":"Huang","year":"2004","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1182\/bloodadvances.2018028886","article-title":"Enhancing the antitumor functions of invariant natural killer T cells using a soluble CD1d-CD19 fusion protein","volume":"3","author":"Das","year":"2019","journal-title":"Blood Adv."},{"key":"ref_74","first-page":"129","article-title":"Increased expression of two alternative spliced variants of CD1d molecule in human gastric cancer","volume":"12","author":"Hafezi","year":"2015","journal-title":"Iran. J. Immunol."},{"key":"ref_75","first-page":"994","article-title":"Sustained activation and tumor targeting of NKT cells using a DC1d-anti-HER2-scFv fusion protein induce antitumor effects in mice","volume":"118","author":"Stirnemann","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1002\/art.23812","article-title":"Modulation of peripheral B cell tolerance by CD72 in a murine model","volume":"58","author":"Li","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.clim.2016.02.004","article-title":"Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis","volume":"164","author":"Vadasz","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Shen, Y., Ma, Y., Xie, J., Lin, L., Shi, Y., Li, X., Shen, P., Pan, X., and Ren, H. (2020). A regulatory role for CD72 expression on B cells and increased soluble CD72 in primary Sjogren\u2019s syndrome. BMC Immunol., 21.","DOI":"10.1186\/s12865-020-00351-2"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Eiza, N., Sabag, A., Kessler, O., Toubi, E., and Vadasz, Z. (2024). Soluble CD72, is a T-cell activator probably via binding to CD6 in homeostasis and autoimmunity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1367120"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7319\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:09:33Z","timestamp":1786968573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,16]]},"references-count":79,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167319"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167319","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,16]]}}}