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Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases
Open accessAbstract
There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.
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Liu, Z., Yang, X., Ji, Y., Wang, S., & Wang, J. (2026) · Frontiers in Reproductive Health · doi:10.3389/frph.2026.1752758 · Cited by 2
“TGF-β functions as an anti inflammatory mediator that constrains the proliferation of immune precursor cells and maintains a balance between pro inflammatory and anti inflammatory signals (83).”
Khorasani, S., Yousefi, M. H., Safarirad, S., Afkhami, H., & Khodadadi, A. (2026) · European journal of medical research · doi:10.1186/s40001-026-04170-w
“IL-5’s stimulatory effects also promote B cell growth [226].”
Akpan, M. M., Ikeji, C. N., Arije, C. M., Mohammed, K. A., Salaudeen, F. A., Adedara, I., Owumi, S., & Farombi, E. (2026) · Immunopharmacology and immunotoxicology · doi:10.1080/08923973.2026.2662624
“…and as well inducing the expression of adhesion molecules [73]. tNF-α is primarily involved in the innate immune response and enhances inflammation by promoting cytokine production [74]. it also induces the expression of cell adhesion molecules and stimulates cell growth and proliferation [75].”
Anti-IL-4Rα antibody SHR-1819 for moderate-to-severe atopic dermatitis: a randomized phase 2 study
Gu, C., Yin, H., Yang, B., Suyun, J. I., Bian, K., Man, X., Lu, J., Sui, D., Zhou, Y., Cheng, F., et al. (2026) · BMC Medicine · doi:10.1186/s12916-026-04952-3
Lima-Silva, M. L., Mambrini, J. V. D. M., Torres, K. C. D. L., Martins‐Filho, O. A., Teixeira-Carvalho, A., Lima-Costa, M. F., & Peixoto, S. V. (2026) · Cadernos de Saúde Pública · doi:10.1590/0102-311xpt172124
“Esse biomar-cador tem um papel chave no desenvolvimento da inflamação, sendo identificado como um fator quimiotático potente e específico para neutrófilos 36,37,38,39 .”
Ming, K., Hu, Y., Xing, B., Chen, M., Chen, Y., Chen, X., Geng, M., Wu, Z., Liu, Y., Wei, L., et al. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103336
“Complete blockade of TNF function is undesirable given its essential roles in anti-infection defense, anti-tumor immunity, and immune homeostasis [69].”
Šútovská, M., Dohál, M., Gondáš, E., Mažerik, J., Švihra, J., Cipková, L., Fraňová, S., & Ľupták, J. (2026) · Cancers · doi:10.3390/cancers18121972
“Tumor Necrosis Factors (TNF) [39] TNF-α (cachectin) Pro-inflammatory and pyrogenic effects; activation of innate immunity; induction of endothelial adhesion molecules; apoptosis; systemic inflammatory response syndrome TNF-β (lymphotoxin-α ) Effects similar to TNF-α TGF-β —transforming growth…”
Li, E., Shi, M., & Huang, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1879430
Хухліна, О. С., Дудка, І. В., Abrahamovych, M. O., & Дудка, Т. В. (2026) · Lviv clinical bulletin · doi:10.25040/lkv2026.02.015
Ramanathan, A., Ghani, W. M. N., Zakaria, S. S., Ripen, Z. M., Gopalan, S., Abidin, M. Z., Rahman, F. A., Ekanayaka, R. P., YEONG, J. P. S., Joseph, C., et al. (2026) · Journal of Clinical Pathology · doi:10.1136/jcp-2025-210609
“36 While high levels of both eosinophils and macrophages can independently be tumouricidal, a high CD66b − CD15 + / CD68 + ratio suggests a deficiency in antitumour M1 TAM, directly weakening the local immune response.”
Wood, O., Braithwaite, A. T., Fisher, J., Li, L., Murray, L., Paluch, C., & Jackson, M. A. (2026) · Genome Medicine · doi:10.1186/s13073-026-01721-y · Cited by 2
“Prior studies have demonstrated similar immuno-regulatory effects of these cytokines, supporting alignment of the data resource with expected effects [60].”
Serum IL2Rα as a Diagnostic Biomarker and Its Functional Interplay With IL‐2 in Breast Cancer
Wang, W., Liu, J., Wei, Y., Yan, F., Ding, S., Liu, D., & Zhu, L. (2026) · The Breast Journal · doi:10.1155/tbj/5295439
“Cytokines of the interleukin (IL) family, including IL-1 β , IL-6, and IL-8, have been implicated in breast cancer pathogenesis, particularly in processes such as bone metastasis and tumor cell proliferation [5, 6].”
Singh, S., Samantha, Sharma, N., Gupta, S., & Kumar, P. (2026) · Letters in Applied NanoBioScience · doi:10.33263/lianbs152.071
“Antigen-presenting cell types and T-cell activation influence the cytokine expression profile [49–53].”
Akim-Shittu, N. O., Peng, G., Tan, Y., Abudouwanli, A., Sun, Q., Yang, M., Zhao, W., Ogawa, H., Okumura, K., & Niyonsaba, F. (2026) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-026-09196-w
“IL-25, also known as IL-17E, is a member of the IL-17 cytokine family but is functionally distinct from other family members because of its pronounced ability to promote type 2 immune responses [14, 64].”
Liu, D., DUCA, E. D., Delaleu, N., Lau, M., Pulsinelli, J., da Rosa, J. C., Bar, J., Estrada, Y. D., Gudjonsson, J. E., Julia, V., et al. (2026) · Allergy · doi:10.1111/all.70505
ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling
Idani, A., Bibi‐Triki, S., Stemmelen, T., Radosavljevic, M., Grenot, P., Hirschler, A., Bernard, A. M., Rosenzwajg, M., Yang, J., Eischen, A., et al. (2026) · Journal of Human Immunity · doi:10.70962/jhi.20250234
Metadata
- Authors
- Akdis, M., Aab, A., Altunbulakli, C., Azkur, K., Costa, R. A., Crameri, R., Duan, S., Eiwegger, T., Eljaszewicz, A., Ferstl, R., Frei, R., Garbani, M., Globinska, A., Hess, L., Huitema, C., Kubo, T., Komlosi, Z., Konieczna, P., Kovacs, N., Kucuksezer, U. C., Meyer, N., Morita, H., Olzhausen, J., O'Mahony, L., Pezer, M., Prati, M., Rebane, A., Rhyner, C., Rinaldi, A., Sokolowska, M., Stanic, B., Sugita, K., Treis, A., van de Veen, W., Wanke, K., Wawrzyniak, M., Wawrzyniak, P., Wirz, O. F., Zakzuk, J. S., & Akdis, C. A.
- Affiliations
- University of Zurich (CH)
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 138
- Issue
- 4
- Pages
- 984-1010
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2517700447
- Cited by
- 912
- References
- 222
- Citations by year
- 2026: 57 · 2025: 117 · 2024: 102 · 2023: 108 · 2022: 119 · 2021: 128 · 2020: 97 · 2019: 75 · 2018: 64 · 2017: 39 · 2016: 4
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Allergy and Clinical Immunology (acceptedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Swiss National Science Foundation (310030_156823, 320030-159870)
- Christine Kühne-Center for Allergy Research and Education (CK-CARE)
- PREDICTA
- European Commission's Seventh Framework programme (260895, 261357)
- GlaxoSmithKline
- European Academy of Allergy and Clinical Immunology
- Global Allergy and Asthma European Network (GA2LEN)
- International Society for Applied Biological Sciences
- Commission for Technology and Innovation
- Novartis
- MeDALL
- Christine Kühne-Center for Allergy Research and Education
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- interleukins, interferon, TGF-beta, TNF-α, cytokine receptors, cytokine signaling pathways, immune regulation, allergy, asthma, autoimmune disease, chronic infection, organ transplantation, carcinogenesis, gene-deficient mice, cytokine gene polymorphisms
- MeSH terms
- Animals, Humans, Immune System Diseases, Interferons, Interleukins, Tumor Necrosis Factor-alpha, Transforming Growth Factor beta, T-Lymphocytes, Regulatory
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