The IL-12 family cytokines in neurodegenerative diseases: dual roles in neurotoxicity and neuroprotection

Al-Shammri S, Chattopadhyay A, Raghupathy R (2025) Vitamin D supplementation mediates a shift toward anti-inflammatory cytokine response in multiple sclerosis. Med Princ Pract. https://doi.org/10.1159/000544106

PubMed  PubMed Central  Google Scholar 

Álvarez-Luquín DD, Arce-Sillas A, Leyva-Hernández J, Sevilla-Reyes E, Boll MC, Montes-Moratilla E, Vivas-Almazán V, Pérez-Correa C, Rodríguez-Ortiz U, Espinoza-Cárdenas R (2019) Regulatory impairment in untreated Parkinson’s disease is not restricted to Tregs: other regulatory populations are also involved. J Neuroinflammation 16:1–11

Google Scholar 

An J, Fu D, Chen X, Guan C, Li L, Bai J, Lv H (2025) Revisiting the role of IL-27 in obesity-related metabolic diseases: safeguard or perturbation? Front Immunol 15:1498288

PubMed  PubMed Central  Google Scholar 

Andreadou M, Ingelfinger F, De Feo D, Cramer TLM, Tuzlak S, Friebel E, Schreiner B, Eede P, Schneeberger S, Geesdorf M, Ridder F, Welsh CA, Power L, Kirschenbaum D, Tyagarajan SK, Greter M, Heppner FL, Mundt S, Becher B (2023) IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice. Nat Neurosci 26(10):1701–1712

CAS  PubMed  PubMed Central  Google Scholar 

Andres-Martin F, James C, Catalfamo M (2024) IL-27 expression regulation and its effects on adaptive immunity against viruses. Front Immunol 15:1395921

CAS  PubMed  PubMed Central  Google Scholar 

Ano Y, Ikado K, Uchida K, Nakayama H (2020) Amyloid β-induced mesenteric inflammation in an Alzheimer’s disease transgenic mouse model. Curr Alzheimer Res 17(1):52–59

CAS  PubMed  Google Scholar 

Avarachan J, Augustine A, Shinde PM, Gunasekaran V (2021) A mechanistic approach of peroxisome proliferator-activated receptors and its subtypes on clinical and preclinical model of neurodegenerative disorders. Res J Pharm Technol 14(7):3967–3975

Google Scholar 

Barac IS, Văcăraș V, Iancu M, Mureșanu DF, Procopciuc LM (2023a) Interleukins (IL-23 and IL-27) serum levels: relationships with gene polymorphisms and disease patterns in multiple sclerosis patients under treatment with interferon and glatiramer acetate. Heliyon. https://doi.org/10.1016/j.heliyon.2023.e17427

PubMed  PubMed Central  Google Scholar 

Barac IS, Văcăraș V, Iancu M, Mureșanu DF, Procopciuc LM (2023b) Interleukins (IL-23 and IL-27) serum levels: relationships with gene polymorphisms and disease patterns in multiple sclerosis patients under treatment with interferon and glatiramer acetate. Heliyon 9(6):e17427

CAS  PubMed  PubMed Central  Google Scholar 

Bastian D, Wu Y, Betts BC, Yu X-Z (2019) The IL-12 cytokine and receptor family in graft-vs.-host disease. Front Immunol 10:988

CAS  PubMed  PubMed Central  Google Scholar 

Beckers L, Baeten P, Popescu V, Swinnen D, Cardilli A, Hamad I, Van Wijmeersch B, Tavernier SJ, Kleinewietfeld M, Broux B, Fraussen J, Somers V (2024) Alterations in the innate and adaptive immune system in a real-world cohort of multiple sclerosis patients treated with ocrelizumab. Clin Immunol 259:109894

CAS  PubMed  Google Scholar 

Benarroch E (2024) What is the role of cytokines in synaptic transmission? Neurology 103(8):e209928

PubMed  Google Scholar 

Bhardwaj V, Kumari S, Dhapola R, Sharma P, Beura SK, Singh SK, Vellingiri B, HariKrishnaReddy D (2025) Shedding light on microglial dysregulation in Alzheimer’s disease: exploring molecular mechanisms and therapeutic avenues. Inflammopharmacology 33(2):679–702

PubMed  Google Scholar 

Bourgonje AR, Ungaro RC, Mehandru S, Colombel JF (2024) Targeting the IL-23 pathway in inflammatory bowel disease. Gastroenterology 168(1):29–52

PubMed  Google Scholar 

Bright F, Werry EL, Dobson-Stone C, Piguet O, Ittner LM, Halliday GM, Hodges JR, Kiernan MC, Loy CT, Kassiou M (2019) Neuroinflammation in frontotemporal dementia. Nat Rev Neurol 15(9):540–555

PubMed  Google Scholar 

Cassatella MA, Gardiman E, Arruda-Silva F, Bianchetto-Aguilera F, Gasperini S, Bugatti M, Vermi W, Larousserie F, Devergne O, Tamassia N (2020) Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39. J Leukoc Biol 108(5):1515–1526

CAS  PubMed  Google Scholar 

Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, Lucian L, Geissler R, Brodie S, Kimball AB (2006) IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 203(12):2577–2587

CAS  PubMed  PubMed Central  Google Scholar 

Chen Z, Balachandran YL, Chong WP, Chan KW (2024) Roles of cytokines in Alzheimer’s disease. Int J Mol Sci 25(11):5803

CAS  PubMed  PubMed Central  Google Scholar 

Choi JK, Egwuagu CE (2021) Interleukin 35 regulatory B cells. J Mol Biol 433(1):166607

CAS  PubMed  Google Scholar 

Choi J, Leung PS, Bowlus C, Gershwin ME (2015) IL-35 and autoimmunity: a comprehensive perspective. Clin Rev Allergy Immunol 49:327–332

CAS  PubMed  Google Scholar 

Chu M, Wen L, Jiang D, Liu L, Nan H, Yue A, Wang Y, Wang Y, Qu M, Wang N (2023) Peripheral inflammation in behavioural variant frontotemporal dementia: associations with central degeneration and clinical measures. J Neuroinflammation 20(1):65

PubMed  PubMed Central  Google Scholar 

Clénet ML, Laurent C, Lemaitre F, Farzam-kia N, Tastet O, Devergne O, Lahav B, Girard M, Duquette P, Prat A (2021) The IL-27/IL-27R axis is altered in CD4+ and CD8+ T lymphocytes from multiple sclerosis patients. Clin Trans Immunol 10(3):e1262

Google Scholar 

Collison LW, Vignali DA (2008) Interleukin-35: odd one out or part of the family? Immunol Rev 226(1):248–262

CAS  PubMed  PubMed Central  Google Scholar 

Dias de Sousa MA, Desidério CS, da Silva Catarino J, Trevisan RO, Alves da Silva DA, Rocha VFR, Bovi WG, Timoteo RP, Bonatti RCF, da Silva AE (2022) Role of cytokines, chemokines and IFN-γ+ IL-17+ double-positive CD4+ T cells in patients with multiple sclerosis. Biomedicines 10(9):2062

CAS  PubMed  PubMed Central  Google Scholar 

Dong C, Tan D, Sun H, Li Z, Zhang L, Zheng Y, Liu S, Zhang Y, He Q (2024) Interleukin-12 delivery strategies and advances in tumor immunotherapy. Curr Issues Mol Biol 46(10):11548–11579

CAS  PubMed  PubMed Central  Google Scholar 

Duffy, S. (2018). The role of regulatory T cells and interleukin-35 in pain associated with an animal model of multiple sclerosis, UNSW Sydney

Dzamko N (2023) Cytokine activity in Parkinson’s disease. Neuronal Signaling. https://doi.org/10.1042/NS20220063

PubMed  PubMed Central  Google Scholar 

Eede P, Obst J, Benke E, Yvon-Durocher G, Richard BC, Gimber N, Schmoranzer J, Böddrich A, Wanker EE, Prokop S (2020) Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer’s disease-like mice. EMBO Rep 21(3):e48530

CAS  PubMed  PubMed Central  Google Scholar 

Ellrichmann G, Reick C, Saft C, Linker RA (2013) The role of the immune system in Huntington’s disease. J Immunol Res 2013(1):541259

Google Scholar 

Erichsen PA, Henriksen EE, Nielsen JE, Ejlerskov P, Simonsen AH, Toft A (2025) Immunological fluid biomarkers in frontotemporal dementia: a systematic review. Biomolecules 15(4):473

CAS  PubMed  PubMed Central  Google Scholar 

Fu J, Huang Y, Bao T, Liu C, Liu X, Chen X (2022) The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A. J Neuroinflammation 19(1):98

CAS  PubMed  PubMed Central  Google Scholar 

Gaimari A, Fusaroli M, Raschi E, Baldin E, Vignatelli L, Nonino F, De Ponti F, Mandrioli J, Poluzzi E (2022) Amyotrophic lateral sclerosis as an adverse drug reaction: a disproportionality analysis of the food and drug administration adverse event reporting system. Drug Saf 45(6):663–673

CAS  PubMed  Google Scholar 

Gałecka M, Bliźniewska-Kowalska K, Orzechowska A, Szemraj J, Maes M, Berk M, Su K-P, Gałecki P (2021) Inflammatory versus anti-inflammatory profiles in major depressive disorders—the role of IL-17, IL-21, IL-23, IL-35 and Foxp3. J Pers Med 11(2):66

PubMed  PubMed Central  Google Scholar 

Gao H, Li K, Ai K, Geng M, Cao Y, Wang D, Yang J, Wei X (2023) Interleukin-12 induces IFN-γ secretion and STAT signaling implying its potential regulation of Th1 cell response in Nile tilapia. Fish Shellfish Immunol 140:108974

CAS  PubMed  Google Scholar 

García-Domínguez M (2025) The role of IL-23 in the development of inflammatory diseases. Biol 14(4):347

Google Scholar 

Gautam AS, Pulivarthi Cb, Singh RK (2023) Proinflammatory IL-17 levels in serum/cerebrospinal fluid of patients with neurodegenerative diseases: a meta-analysis study. Naunyn Schmiedebergs Arch Pharmacol 396(3):577–588

CAS  PubMed  Google Scholar 

Gaviglio EA, Peralta Ramos JM, Arroyo DS, Bussi C, Iribarren P, Rodriguez-Galan MC (2022a) Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain. Int Immunopharmacol 105:108546

CAS  PubMed  PubMed Central 

Comments (0)

No login
gif