Expanding diversity in molecular structures and functions of the IL-6/IL-12 heterodimeric cytokine family
Open accessAbstract
The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they are composed of two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than 6 cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12 (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein-Barr virus-induced protein 3 (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3). This family of cytokines covers a very broad range of immune responses, including pro-inflammatory responses such as helper T (Th)1, Th2, and Th17 to anti-inflammatory responses such as regulatory T (Treg) cells and IL-10-producing Treg cells. IL-12 is the first member of this family, and IL-12, IL-23, and IL-27 are mainly produced by activated antigen-presenting cells such as dendritic cells and macrophages. IL-12 plays a critical role in the promotion of Th1 immune responses by inducing interferon-γ production to combat pathogens and malignant tumors. IL-23 induces IL-17 production and is necessary to maintain pathogenic Th17 cells that cause inflammatory and autoimmune diseases. IL-27 was initially reported to play a critical role in promotion of Th1 differentiation; however, subsequent studies revealed that IL-27 has broader stimulatory and inhibitory roles by inducing IL-10-producing Treg cells. IL-35 is produced by forkhead box P3+ Treg cells and activated B cells and has immunosuppressive functions to maintain immune tolerance. The most recently identified cytokine, IL-39, is produced by activated B cells and has pro-inflammatory functions. The cytokine tentatively named IL-Y seems to have anti-inflammatory functions by inhibiting Th1 and Th17 differentiation. In addition, individual cytokine subunits were also shown to have self-standing activities. Thus, promiscuity within the IL-6/IL-12 family cytokines complicates structural and functional clarification and assignment of individual cytokines. A better understanding of the recent advances and expanding diversity in molecular structures and functions of the IL-6/IL-12 family cytokines could allow the creation of novel therapeutic strategies by using them as tools and targeted molecules.
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IL-6 is a pleiotropic cytokine involved in immune responses, inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes.
“IL-6, which was discovered in 1986 (27), is a pleiotropic cytokine involved not only in immune responses but also in inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes (1, 21, 28–32).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [32]
The Introduction describes IL-6 as an important inflammatory cytokine, and the Abstract describes pleiotropic immune functions of the IL-6/IL-12 family. The copy does not establish the claimed roles of IL-6 specifically in hematopoiesis, bone metabolism, or embryonic development; its hematopoiesis discussion concerns IL-27. (LLM, conf=0.86)
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IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“IL-6, which was discovered in 1986 (27), is a pleiotropic cytokine involved not only in immune responses but also in inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes (1, 21, 28–32).”
BackgroundThe cytokine network involved in the host immune response to periodontitis
Pan, W., Wang, Q., & Chen, Q. (2019) · International Journal of Oral Science · doi:10.1038/s41368-019-0064-z · Cited by 709 · see citing works
Pleiotropy and specificity: insights from the interleukin 6 family of cytokines
Murakami, M., Kamimura, D., & Hirano, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.027 · Cited by 533 · see citing works
Historical overview of the interleukin-6 family cytokine
Kang, S., Narazaki, M., Metwally, H., & Kishimoto, T. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20190347 · Cited by 360 · see citing works
IL-12 Family Cytokines in Cancer and Immunotherapy
Mirlekar, B., & Pylayeva‐Gupta, Y. (2021) · Cancers · doi:10.3390/cancers13020167 · Cited by 296 · see citing works
Deodhar, A. A., Gottlieb, A. B., Boehncke, W., Dong, B., Wang, Y., Zhuang, Y., Barchuk, W., Xu, X. L., Hsia, E. C., Aelion, J. A., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30952-8 · Cited by 182 · see citing works
Cytokine Response to Exercise and Its Modulation
Suzuki, K. (2018) · Antioxidants · doi:10.3390/antiox7010017 · Cited by 139 · see citing works
Bloch, Y., Bouchareychas, L., Merceron, R., Składanowska, K., den Bossche, L. V., Detry, S., Govindarajan, S., Elewaut, D. S., Haerynck, F., Dullaers, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.12.008 · Cited by 136 · see citing works
The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease
Acevedo, G. R., Girard, M. C., & Gómez, K. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01929 · Cited by 130 · see citing works
Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases
Cheng, Y., Yano, H., Workman, C. J., & Vignali, D. A. A. (2021) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2021.0147 · Cited by 126 · see citing works
Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy
Bridgewood, C., Sharif, Κ., Sherlock, J. P., Watad, ., & McGonagle, D. (2020) · Immunological Reviews · doi:10.1111/imr.12840 · Cited by 120 · see citing works
Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation?
Siebert, S., Millar, N. L., & McInnes, I. B. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-213654 · Cited by 100 · see citing works
IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer
Kourko, O., Seaver, K., Odoardi, N., Basta, S., & Gee, K. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00969 · Cited by 94 · see citing works
Hung, Y.-L., Wang, S.-C., Suzuki, K., Fang, S.-H., Chen, C.-S., Cheng, W.-C., Su, C.-C., Yeh, H.-C., Tu, H., Liu, P.-L., et al. (2019) · Phytomedicine · doi:10.1016/j.phymed.2018.12.008 · Cited by 81 · see citing works
Update on the etiopathogenesis of psoriasis (Review)
Branisteanu, D. E., Cojocaru, C., Diaconu, R., Porumb‐Andrese, E., Alexa, A. I., Nicolescu, A. C., Brihan, I., Bogdănici, C. M., Brănișteanu, G., Dimitriu, A., et al. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11124 · Cited by 85 · see citing works
Visvanathan, S., Baum, P., Vinisko, R., Schmid, R., Flack, M., Lalovic, B. B., Kleiner, O., Fuentes‐Duculan, J., Garcet, S., Davis, J. W., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.11.042 · Cited by 74 · see citing works
Roles of Cytokines in Alzheimer’s Disease
Chen, Z., Balachandran, Y. L., Chong, W. P., & Chan, K. W. Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115803 · Cited by 71 · see citing works
Reich, K., Papp, K. A., Armstrong, A. W., Wasfi, Y. S., Li, S., Shen, Y., Randazzo, B. P., Song, M., & Kimball, A. B. (2018) · British Journal of Dermatology · doi:10.1111/bjd.17454 · Cited by 69 · see citing works
IL-12 and IL-23—Close Relatives with Structural Homologies but Distinct Immunological Functions
Floss, D. M., Moll, J. M., & Scheller, J. (2020) · Cells · doi:10.3390/cells9102184 · Cited by 68 · see citing works
Current Insights in Genetics of Sarcoidosis: Functional and Clinical Impacts
Calender, A., Weichhart, T., Valeyre, D., & Pachéco, Y. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082633 · Cited by 66 · see citing works
Cytokines and their role as immunotherapeutics and vaccine Adjuvants: The emerging concepts
Rahman, T., Das, A., Abir, M. H., Nafiz, I. H., Mahmud, A. R., Sarker, M. R., Emran, T. B., & Hassan, M. M. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156268 · Cited by 61 · see citing works
Effect of Exercise Intensity on Cell-Mediated Immunity
Suzuki, K., & Hayashida, H. (2021) · Sports · doi:10.3390/sports9010008 · Cited by 58 · see citing works
Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis
Guo, K., & Zhang, X. (2021) · Journal of Immunology Research · doi:10.1155/2021/6693542 · Cited by 54 · see citing works
Espígol‐Frigolé, G., Planas‐Rigol, E., Lozano, E., Corbera‐Bellalta, M., Terrades-García, N., Prieto‐González, S., García‐Martínez, A., Hernández‐Rodríguez, J., Grau, J. M., & Cid, M. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00809 · Cited by 51 · see citing works
The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis
Bello, R. O., Chin, V. K., Isnadi, M. F. A. R., Majid, R. A., Abdullah, M. A., Lee, T. Y., Zakaria, Z. A., Hussain, M. K., & Basir, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041149 · Cited by 47 · see citing works
Human neutrophils activated via TLR8 promote Th17 polarization through IL-23
Tamassia, N., Arruda-Silva, F., Wright, H. L., Moots, R. J., Gardiman, E., Bianchetto-Aguilera, F. M., Gasperini, S., Capone, M., Maggi, L., Annunziato, F., et al. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.ma0818-308r · Cited by 47 · see citing works
Interleukin 39: a new member of interleukin 12 family
Lu, Z., Xu, K., Wang, X., Li, Y., & Li, M. (2020) · Central European Journal of Immunology · doi:10.5114/ceji.2020.97911 · Cited by 45 · see citing works
The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man
Bridgewood, C., Alase, A. A., Watad, ., Wittmann, M., Cuthbert, R., & McGonagle, D. (2019) · Inflammation Research · doi:10.1007/s00011-019-01235-x · Cited by 44 · see citing works
Chen, I., Wang, S., Chen, Y., Tseng, H.-H., Liu, P., Lin, T.-C., Wu, H., Chen, Y.-R., Tseng, Y., Hsu, J., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14101046 · Cited by 40 · see citing works
Guillot, A., Gasmi, I., Brouillet, A., Ait‐Ahmed, Y., Calderaro, J., Ruiz, I., Gao, B., Lotersztajn, S., Pawlotsky, J., & Lafdil, F. (2018) · Hepatology Communications · doi:10.1002/hep4.1145 · Cited by 38 · see citing works
Floss, D. M., Schönberg, M., Franke, M., Horstmeier, F. C., Engelowski, E., Schneider, A., Rosenfeldt, E. M., & Scheller, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-15173-3 · Cited by 38 · see citing works
IL-27, but not IL-35, inhibits neuroinflammation through modulating GM-CSF expression
Casella, G., Finardi, A., Descamps, H. C., Colombo, F., Maiorino, C., Ruffini, F., Patrone, M., Degano, M., Martino, G., Muzio, L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-16702-w · Cited by 38 · see citing works
IL-12 family cytokines and autoimmune diseases: A potential therapeutic target?
Cui, X., Liu, W., Jiang, H., Zhao, Q., Hu, Y., Tang, X., Liu, X., Dai, H., Rui, H., & Liu, B. (2024) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2024.100263 · Cited by 38 · see citing works
Lim, K., Yong, Z. W. E., Wang, H., Tan, T. Z., Huang, R. Y., Yamamoto, D., Inaki, N., Hazawa, M., Wong, R. W.-C., Oshima, H., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012943 · Cited by 37 · see citing works
Cytokines in Thyroid-Associated Ophthalmopathy
Zhang, P., & Zhu, H. (2022) · Journal of Immunology Research · doi:10.1155/2022/2528046 · Cited by 35 · see citing works
SOCS molecules: the growing players in macrophage polarization and function
Zhou, D., Chen, L., Yang, K., Jiang, H., Xu, W., & Luan, J. (2017) · Oncotarget · doi:10.18632/oncotarget.19940 · Cited by 35 · see citing works
Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients
Monserrat, J., Gomez-Lahoz, A. M., Ortega, M. A., Sanz, J., Muñoz, B., Arévalo‐Serrano, J., González-Moro, J. M. R., Gasalla-Herraiz, J., Gasulla, Ó., Arranz, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810344 · Cited by 31 · see citing works
Local Cytokine Expression Profiling in Patients with Specific Autoimmune Uveitic Entities
El‐Asrar, A. M. A., Berghmans, N., Al‐Obeidan, S. A., Gikandi, P. W., Opdenakker, G., Damme, J. V., & Struyf, S. (2019) · Ocular Immunology and Inflammation · doi:10.1080/09273948.2019.1604974 · Cited by 31 · see citing works
Recent Insights into CD4+ Th Cell Differentiation in Malaria
Soon, M. S. F., & Haque, A. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701316 · Cited by 30 · see citing works
Revisiting the combinatorial potential of cytokine subunits in the IL-12 family
Detry, S., Składanowska, K., Vuylsteke, M., Savvides, S. N., & Bloch, Y. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.03.026 · Cited by 31 · see citing works
Stein, T., Wollschlegel, A., Té, H., Weiss, J., Joshi, K., Kinzel, B., Billich, A., Guntermann, C., & Lehmann, J. (2018) · FEBS Journal · doi:10.1111/febs.14600 · Cited by 29 · see citing works
An emerging role of interleukin-23 in rheumatoid arthritis
Yuan, N., Yu, G., Liu, D., Wang, X., & Zhao, L. (2019) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2019.1610429 · Cited by 29 · see citing works
The IL-12 family cytokines in fish: Molecular structure, expression profile and function
Wang, X., Zhang, A., Qiu, X., YANG, K. Y., & Zhou, H. Y. (2023) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2023.104643 · Cited by 28 · see citing works
Lessons on SpA pathogenesis from animal models
Bréban, M., Glatigny, S., Cherqaoui, B., Beaufrère, M., Lauraine, M., Rincheval‐Arnold, A., Gaumer, S., Guénal, I., & Araujo, L. M. M. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-020-00832-x · Cited by 26 · see citing works
Assembly-induced folding regulates interleukin 12 biogenesis and secretion
Reitberger, S., Haimerl, P., Aschenbrenner, I., Bieren, J. E., & Feige, M. J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.782284 · Cited by 26 · see citing works
The Role of IL-23 in the Development of Inflammatory Diseases
García-Domínguez, M. (2025) · Biology · doi:10.3390/biology14040347 · Cited by 33 · see citing works
Lack of evidence for expression and function of IL-39 in human immune cells
Ecoeur, F., Weiss, J., Schleeger, S., & Guntermann, C. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242329 · Cited by 25 · see citing works
Manolova, I., Ivanova, M. G., Vasilev, G., Stoilov, R. M., Miteva, L. D., & Stanilova, S. A. (2019) · Immunological Investigations · doi:10.1080/08820139.2019.1622561 · Cited by 23 · see citing works
Diao, H.-Y., Zhu, W., Liu, J., Yin, S., Wang, J., & Li, C. (2023) · Molecules · doi:10.3390/molecules28083630 · Cited by 23 · see citing works
Yang, M.-G., Tian, S., Zhang, Q., Han, J., Liu, C., Zhou, Y., Zhu, J., & Jin, T. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102430 · Cited by 22 · see citing works
Association of single-nucleotide polymorphisms in the IL27 gene with autoimmune thyroid diseases
He, W., Wang, B., Mu, K., Zhang, J., Yanping, Y., Yao, W., Li, S., & Zhang, J. (2019) · Endocrine Connections · doi:10.1530/ec-18-0370 · Cited by 22 · see citing works
A new class of biologic agents facing the therapeutic paradigm in psoriasis: anti-IL-23 agents.
Tonini, A., Gualtieri, B., Panduri, S., Romanelli, M., & Chiricozzi, A. (2017) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1398729 · Cited by 21 · see citing works
A review of signaling and transcriptional control in T follicular helper cell differentiation
Hart, A. P., & Laufer, T. M. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ri0121-066r · Cited by 19 · see citing works
A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions
Watanabe, A., Mizoguchi, I., Hasegawa, H., Katahira, Y., Inoué, S., Sakamoto, E., Furusaka, Y., Sekine, A., Miyakawa, S., Murakami, F., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.757669 · Cited by 21 · see citing works
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Guselkumab for the treatment of adults with moderate to severe plaque psoriasis
Puig, L. (2019) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1601014 · Cited by 18 · see citing works
Ahmed, H. A., Maklad, A. M., Khaled, S. A. A., & Elyamany, A. M. (2019) · Journal of Blood Medicine · doi:10.2147/jbm.s221301 · Cited by 18 · see citing works
Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects
Rybchenko, V. S., Aliev, T. K., Панина, А. А., Kirpichnikov, M. P., & Dolgikh, D. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020336 · Cited by 18 · see citing works
Mora‐Boza, A., Ghebrezadik, S. G., Leisen, J., & Garcı́a, A. J. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202300942 · Cited by 18 · see citing works
Ghavami, A., Fathpour, G., & Amirghofran, Z. (2017) · Pathology & Oncology Research · doi:10.1007/s12253-017-0295-2 · Cited by 18 · see citing works
Cassatella, M. A., Gardiman, E., Arruda-Silva, F., Bianchetto-Aguilera, F. M., Gasperini, S., Bugatti, M., Vermi, W., Larousserie, F., Devergne, O., & Tamassia, N. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma0520-054r · Cited by 18 · see citing works
Structural Basis of Activation and Antagonism of Receptor Signaling Mediated by Interleukin-27
Składanowska, K., Bloch, Y., Strand, J., White, K., Hua, J., Aldridge, D. L., Welin, M., Logan, D. T., Soete, A., Merceron, R., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111490 · Cited by 15 · see citing works
Yadav, M. K., Singh, S. P., & Egwuagu, C. E. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1514080 · Cited by 15 · see citing works
Guselkumab in the treatment of moderate-to-severe plaque psoriasis
López‐Sánchez, C., & Puig, L. (2020) · Immunotherapy · doi:10.2217/imt-2020-0040 · Cited by 15 · see citing works
Have Therapeutics Enhanced Our Knowledge of Axial Spondyloarthritis?
Harrison, S. R., & Marzo‐Ortega, H. (2023) · Current Rheumatology Reports · doi:10.1007/s11926-023-01097-7 · Cited by 14 · see citing works
Naturally occurring and synthetic constitutive-active cytokine receptors in disease and therapy
Floss, D. M., & Scheller, J. (2019) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2019.05.007 · Cited by 14 · see citing works
Huang, F., Ju, Y.-H., Wang, H., & Li, Y.-N. (2020) · Allergy Asthma and Clinical Immunology · doi:10.1186/s13223-020-00487-1 · Cited by 14 · see citing works
Lay, C. S., Bridges, A. M., Goulding, J., Briddon, S. J., Soloviev, Z., Craggs, P. D., & Hill, S. J. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.05.002 · Cited by 14 · see citing works
Shukri, N. D. M., Izati, A. F., Ghazali, W. S. W., Hussin, C. M. C., & Wong, K. K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.675250 · Cited by 14 · see citing works
Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis
Posadas‐Sánchez, R., & Vargas‐Alarcón, G. (2018) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.17002335 · Cited by 14 · see citing works
Wang, X., Qin, L., Du, L., Chen, D., Zhang, A., YANG, K. Y., & Zhou, H. Y. (2017) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2017.10.009 · Cited by 13 · see citing works
Cid, M. C., Garcés, R. R., Terrades-García, N., & Espígol‐Frigolé, G. (2019) · Lara D. Veeken · doi:10.1093/rheumatology/kez645 · Cited by 13 · see citing works
Interleukin-39 exacerbates concanavalin A-induced liver injury
Li, Y., Gong, L., Weng, L., Pan, X., Liu, C., & Li, M. (2021) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2020.1869778 · Cited by 13 · see citing works
Zhou, L., Tang, C., Li, X., & Feng, F. (2022) · Scientific Reports · doi:10.1038/s41598-022-24189-3 · Cited by 13 · see citing works
Risankizumab for the treatment of moderate to severe psoriasis
Chiricozzi, A., Antonioli, L., Panduri, S., Fornai, M., Romanelli, M., & Blandizzi, C. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1551354 · Cited by 13 · see citing works
Saha, B., Bhattacharjee, S., Sarkar, A., Bhor, R. D., Pai, K. R., & Bodhale, N. P. (2020) · Cytokine · doi:10.1016/j.cyto.2020.155304 · Cited by 12 · see citing works
Zhang, H., Jiang, H.-L., & Dai, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.818413 · Cited by 12 · see citing works
Jiang, C., Chen, W., Yang, Y., Li, X., Jin, M., Ghonaim, A. H., Li, S., & Ren, M. (2024) · Microorganisms · doi:10.3390/microorganisms12122396 · Cited by 12 · see citing works
Hasegawa, H., Mizoguchi, I., Orii, N., Inoué, S., Katahira, Y., Yoneto, T., Xu, M., Miyazaki, T., & Yoshimoto, T. (2021) · Scientific Reports · doi:10.1038/s41598-021-84624-9 · Cited by 12 · see citing works
Self-citationChen, Q., Zhang, Z., Chen, S., Chen, J., Cheng, Y., Liu, A., Li, B., Chen, Z., Zheng, Y., Ga, M., et al. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.615405 · Cited by 12 · see citing works
The role of IL-39 in autoimmune diseases: From general to immunopathogenesis.
Ahmadi, P., Janzadeh, A., Honardoost, M., Taherkhani, S., Doyle, D., & Mojarad, N. (2025) · Cytokine · doi:10.1016/j.cyto.2025.156969 · Cited by 12 · see citing works
EBV-induced gene 3 augments IL-23Rα protein expression through a chaperone calnexin
Mizoguchi, I., Ohashi, M., Hasegawa, H., Chiba, Y., Orii, N., Inoué, S., Kawana, C., Xu, M., Sudo, K., Fujita, K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci122732 · Cited by 11 · see citing works
Self-citationInflammatory Process and Role of Cytokines in Inflammation: An Overview
Muzamil, A., Tahir, H. M., Ali, S., Liaqat, I., Ali, A., & Summer, M. (2022) · Punjab University journal of zoology · doi:10.17582/journal.pujz/2021.36.2.237.252 · Cited by 10 · see citing works
Singh, M., & Venkatas, J. (2022) · Current Cancer Drug Targets · doi:10.2174/1568009622666220609115109 · Cited by 9 · see citing works
Ferrucci, V., Miceli, M., Pagliuca, C., Bianco, O., Castaldo, L., Izzo, L., Cozzolino, M., Zannella, C., Oglio, F., Polcaro, A., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05378-2 · Cited by 10 · see citing works
Effects of active and passive smoking on salivary cytokines levels in rats: A pilot study
Ge, S., Ye, P., Li, G., Fu, Y.-F., Zhou, Q., Huang, F., Wang, X., & Wang, W. (2018) · Toxicology and Industrial Health · doi:10.1177/0748233718817192 · Cited by 10 · see citing works
Cytokines, Their Receptors and Signals
Oppenheim, J. J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812102-3.00015-4 · Cited by 10 · see citing works
Ebi3 Binding to IFN-γ and IL-10 Limits Their Function
Scott, E. N., Ye, C., Yano, H., Lipatova, Z., Brunazzi, E. A., Vignali, K. M., Workman, C. J., & Vignali, D. A. A. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2400236 · Cited by 9 · see citing works
Interleukin-12: Structure, Function, and Its Impact in Colorectal Cancer
Zhu, Z., Peng, Q., Duan, X., & Li, J. (2024) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2023.0190 · Cited by 9 · see citing works
Hu, J., Qin, Y., Yi, S., Wang, C., Yang, J., Yang, L., Wang, L., Kijlstra, A., Yang, P., & Li, H. (2018) · Ocular Immunology and Inflammation · doi:10.1080/09273948.2018.1433306 · Cited by 9 · see citing works
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Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease
Fonseca‐Camarillo, G., Furuzawa‐Carballeda, J., Barreto‐Zúñiga, R., Martínez‐Benítez, B., & Yamamoto-Furusho, J. K. (2023) · Immunologic Research · doi:10.1007/s12026-023-09432-x · Cited by 8 · see citing works
Interleukin-12p40 variant form reduces Interleukin-12p80 secretion
Oshikiri, Y., Nara, H., Takeda, Y., Araki, A., Nemoto, N., Gazi, M. Y., Saito, S., Saitoh, S., Nakajima, O., & Asao, H. (2019) · Cytokine · doi:10.1016/j.cyto.2019.05.017 · Cited by 8 · see citing works
Interleukin-27 in Tuberculosis: A Sheep in Wolf’s Clothing?
Ritter, K., Rousseau, J., & Hölscher, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.810602 · Cited by 8 · see citing works
Dichotomous roles of IL-36 and IL-38 in cardiovascular disease
Zhang, H., Huang, W., & Bao, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1642116 · Cited by 7 · see citing works
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Immunological effects of different types of synthetic CpG oligodeoxynucleotides on porcine cells
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- Authors
- Hasegawa, H., Mizoguchi, I., Chiba, Y., Ohashi, M., Xu, M., & Yoshimoto, T.
- Affiliations
- Tokyo Medical University (JP)
- Corresponding author
- Yoshimoto, Takayuki
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2016-11-04
- Volume
- 7
- Pages
- 479-479
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5095122
- OpenAlex
- W2548333195
- Cited by
- 142
- References
- 79
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 16 · 2023: 14 · 2022: 13 · 2021: 16 · 2020: 16 · 2019: 17 · 2018: 22 · 2017: 9
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (16J04160, 15K07947, 15K08433)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- heterodimeric cytokine, IL-12, IL-23, IL-27, IL-35, IL-39, p40 subunit, EBI3, Th1 cells, Th17 cells, regulatory T cells, IL-10, interferon-gamma, IL-17, dendritic cells, macrophages
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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