Suppressor of cytokine signalling (SOCS) proteins bind to certain cytokine receptors, Janus kinases and signalling molecules to regulate signalling pathways, thus controlling immune and inflammatory responses. Dysregulated expression of various types of SOCS molecules was indicated in multiple types of allergic diseases. SOCS1, SOCS2, SOCS3, SOCS5, and cytokine-inducible SH2 domain protein (CISH) can differentially exert anti-allergic impacts through different mechanisms, such as suppressing Th2 cell development and activation, reducing eosinophilia, decreasing IgE production, repressing production of pro-allergic chemokines, promoting Treg cell differentiation and activation, suppressing Th17 cell differentiation and activation, increasing anti-allergic Th1 responses, inhibiting M2 macrophage polarization, modulating survival and development of mast cells, reducing pro-allergic activity of keratinocytes, and suppressing pulmonary fibrosis. Although some anti-allergic effects were attributed to SOCS3, it can perform pro-allergic impacts through several pathways, such as promoting Th2 cell development and activation, supporting eosinophilia, boosting pro-allergic activity of eosinophils, increasing IgE production, enhancing the expression of the pro-allergic chemokine receptor, reducing Treg cell differentiation, increasing pro-allergic Th9 responses, as well as supporting mucus secretion and collagen deposition. In this review, we discuss the contrasting roles of SOCS proteins in contexts of allergic disorders to provide new insights regarding the pathophysiology of these diseases and possibly explore SOCS proteins as potential therapeutic targets for alleviating allergies.

Department of Hematology and Laboratory Sciences School of Para Medicine Kerman University of Medical Sciences Kerman Iran

Department of Immunology School of Medicine Kerman University of Medical Sciences Kerman Iran

Department of Immunology School of Medicine Rafsanjan University of Medical Sciences Rafsanjan Iran

Department of Microbiology and Immunology Keio University School of Medicine Tokyo Japan

Faculty of Science University of South Bohemia České Budějovice Czech Republic

Immunology of Infectious Diseases Research Center Research Institute of Basic Medical Sciences Rafsanjan University of Medical Sciences Rafsanjan Iran

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

Student Research Committee School of Medicine Kerman University of Medical Sciences Kerman Iran

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Aldakheel FM. Allergic diseases: a comprehensive review on risk factors, immunological mechanisms, link with COVID-19, potential treatments, and role of allergen bioinformatics. Int J Environ Res Public Health. 2021;18(22):12105.

Haider S, Simpson A, Custovic A. Genetics of asthma and allergic diseases. Handb Exp Pharmacol. 2022;268:313-329.

Simon D. Recent advances in clinical allergy and immunology. Int Arch Allergy Immunol. 2018;177(4):324-333.

Chuang YH, Yang YH, Wu SJ, Chiang BL. Gene therapy for allergic diseases. Curr Gene Ther. 2009;9(3):185-191.

Nur Husna SM, Tan HT, Md Shukri N, Mohd Ashari NS, Wong KK. Allergic rhinitis: a clinical and pathophysiological overview. Front Med. 2022;9:874114.

Hesse L, Oude Elberink JNG, van Oosterhout AJM, Nawijn MC. Allergen immunotherapy for allergic airway diseases: use lessons from the past to design a brighter future. Pharmacol Ther. 2022;237:108115.

Lin H, Casale TB. Treatment of allergic asthma. Am J Med. 2002;113(Suppl 9A):8s-16s.

La Rosa M, Lionetti E, Reibaldi M, et al. Allergic conjunctivitis: a comprehensive review of the literature. Ital J Pediatr. 2013;39:18.

Nowicki RJ, Trzeciak M, Kaczmarski M, et al. Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the polish dermatological society, polish Society of Allergology, polish pediatric society and polish Society of Family Medicine. Part I prophylaxis, topical treatment and phototherapy. Postepy Dermatol Alergol. 2020;37(1):1-10.

Zuberbier T. Classification of urticaria. Indian J Dermatol. 2013;58(3):208-210.

Patel BY, Volcheck GW. Food allergy: common causes, diagnosis, and treatment. Mayo Clin Proc. 2015;90(10):1411-1419.

Poziomkowska-Gęsicka I, Kurek M. Clinical manifestations and causes of anaphylaxis. Analysis of 382 cases from the anaphylaxis registry in West Pomerania Province in Poland. Int J Environ Res Public Health. 2020;17(8):2787.

Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H. SOCS, inflammation, and autoimmunity. Front Immunol. 2012;3:20.

Xin P, Xu X, Deng C, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol. 2020;80:106210.

Sobah ML, Liongue C, Ward AC. SOCS proteins in immunity, inflammatory diseases, and immune-related cancer. Front Med. 2021;8:727987.

Vitte J, Vibhushan S, Bratti M, Montero-Hernandez JE, Blank U. Allergy, anaphylaxis, and nonallergic hypersensitivity: IgE, mast cells, and beyond. Medl Princ Pract. 2022;31(6):501-515.

Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693-704.

Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454(7203):445-454.

Martín-Cruz L, Sevilla-Ortega C, Angelina A, et al. From trained immunity in allergy to trained immunity-based allergen vaccines. Clin Exp Allergy. 2023;53(2):145-155.

Palomares Ó, Sánchez-Ramón S, Dávila I, et al. dIvergEnt: how IgE Axis contributes to the continuum of allergic asthma and anti-IgE therapies. Int J Mol Sci. 2017;18(6):1328.

Zheng H, Zhang Y, Pan J, et al. The role of type 2 innate lymphoid cells in allergic diseases. Front Immunol. 2021;12:12.

Gurram RK, Zhu J. Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses. Cell Mol Immunol. 2019;16(3):225-235.

Jin J, Sunusi S, Lu H. Group 2 innate lymphoid cells (ILC2s) are important in typical type 2 immune-mediated diseases and an essential therapeutic target. J Int Med Res. 2022;50(1):3000605211053156.

Duncan SA, Baganizi DR, Sahu R, Singh SR, Dennis VA. SOCS proteins as regulators of inflammatory responses induced by bacterial infections: a review. Front Microbiol. 2017;8:2431.

Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15(1):23.

Low ZY, Wen Yip AJ, Chow VTK, Lal SK. The suppressor of cytokine Signalling family of proteins and their potential impact on COVID-19 disease progression. Rev Med Virol. 2021;32:e2300.

Jafarzadeh A, Nemati M, Jafarzadeh S, Chauhan P, Saha B. The immunomodulatory potentials of interleukin-27 in airway allergies. Scand J Immunol. 2021;93(2):e12959.

Mostecki J, Cassel SL, Klimecki WT, et al. A SOCS-1 promoter variant is associated with total serum IgE levels. J Immunol. 2011;187(5):2794-2802.

Harada M, Nakashima K, Hirota T, et al. Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma. Am J Respir Cell Mol Biol. 2007;36(4):491-496.

Fujimoto M, Tsutsui H, Yumikura-Futatsugi S, et al. A regulatory role for suppressor of cytokine signaling-1 in T(h) polarization in vivo. Int Immunol. 2002;14(11):1343-1350.

Lee C, Kolesnik TB, Caminschi I, et al. Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response. Clin Exp. 2009;39(6):897-907.

Tanaka K, Ichiyama K, Hashimoto M, et al. Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN-gamma on STAT3 and Smads. J Immunol. 2008;180(6):3746-3756.

Yoshimura A, Naka T, Kubo M. SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol. 2007;7(6):454-465.

Takahashi R, Nishimoto S, Muto G, et al. SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-{gamma} and IL-17A production. J Exp Med. 2011;208(10):2055-2067.

Doran E, Choy DF, Shikotra A, et al. Reduced epithelial suppressor of cytokine signalling 1 in severe eosinophilic asthma. Eur Respir J. 2016;48(3):715-725.

Simpson LJ, Patel S, Bhakta NR, et al. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat Immunol. 2014;15(12):1162-1170.

Wang WW, Zhu K, Yu HW, Pan YL. Interleukin-17A potentiates interleukin-13-induced eotaxin-3 production by human nasal epithelial cells from patients with allergic rhinitis. Int Forum Allergy Rhinol. 2019;9(11):1327-1333.

Heller NM, Matsukura S, Georas SN, et al. Interferon-gamma inhibits STAT6 signal transduction and gene expression in human airway epithelial cells. Am J Respir Cell Mol Biol. 2004;31(5):573-582.

Zu Y, Li CR, Zheng YJ, Deng JK, Fu XL. The role of CD4+ CD25+ regulatory T cells in the pathogenesis of asthma in children. Zhonghua Yi Xue Za Zhi. 2006;86(1):35-38.

Ma L, Xue HB, Wang F, Shu CM, Zhang JH. MicroRNA-155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells. Clin Exp Immunol. 2015;181(1):142-149.

McCormick SM, Gowda N, Fang JX, Heller NM. Suppressor of cytokine signaling (SOCS)1 regulates interleukin-4 (IL-4)-activated insulin receptor substrate (IRS)-2 tyrosine phosphorylation in monocytes and macrophages via the proteasome. J Biol Chem. 2016;291(39):20574-20587.

Martinez-Nunez RT, Louafi F, Sanchez-Elsner T. The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1). J Biol Chem. 2011;286(3):1786-1794.

Royce SG, Cheng V, Samuel CS, Tang ML. The regulation of fibrosis in airway remodeling in asthma. Mol Cell Endocrinol. 2012;351(2):167-175.

Nakashima T, Yokoyama A, Onari Y, et al. Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis. J Allergy Clin Immunol. 2008;121(5):1269-1276.

Gielen V, Sykes A, Zhu J, et al. Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons. J Allergy Clin Immunol. 2015;136(1):177-188.e11.

Guan Y, Ma Y, Tang Y, Liu X, Zhao Y, An L. MiRNA-221-5p suppressed the Th17/Treg ratio in asthma via RORγt/Foxp3 by targeting SOCS1. Allergy Asthma Clin Immunol. 2021;17(1):123.

Hui Y, Xie JJ, Li L, et al. Association between suppressors of cytokine signaling mRNA expression and Th1/Th2 balance in children with asthma. Zhongguo Dang Dai er Ke Za Zhi. 2012;14(10):755-758.

Yamamoto K, Yamaguchi M, Miyasaka N, Miura O. SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit. Biochem Biophys Res Commun. 2003;310(4):1188-1193.

Kubo M, Inoue H. Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia. Curr Allergy Asthma Rep. 2006;6(1):32-39.

Takatori H, Nakajima H, Kagami S, et al. Stat5a inhibits IL-12-induced Th1 cell differentiation through the induction of suppressor of cytokine signaling 3 expression. J Immunol. 2005;174(7):4105-4112.

Chen Z, Laurence A, Kanno Y, et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A. 2006;103(21):8137-8142.

Lan F, Zhang N, Zhang J, et al. Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3. J Allergy Clin Immunol. 2013;132(6):1314-1321.

Pillemer BB, Xu H, Oriss TB, Qi Z, Ray A. Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3-mediated suppression of Treg function. Eur J Immunol. 2007;37(8):2082-2089.

Kinjyo I, Inoue H, Hamano S, et al. Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J Exp Med. 2006;203(4):1021-1031.

Nakaya M, Hashimoto M, Nakagawa R, et al. SOCS3 in T and NKT cells negatively regulates cytokine production and ameliorates ConA-induced hepatitis. J Immunol. 2009;183(11):7047-7053.

Jannat A, Khan M, Shabbir M, Badshah Y. Expression of suppressor of cytokine signaling 3 (SOCS3) and interleukin-6 (−174-G/C) polymorphism in atopic conditions. PloS One. 2019;14(6):e0219084.

Hartgers FC, Obeng BB, Kruize YC, et al. Lower expression of TLR2 and SOCS-3 is associated with Schistosoma haematobium infection and with lower risk for allergic reactivity in children living in a rural area in Ghana. PLoS Negl Trop Dis. 2008;2(4):e227.

Almeida-Oliveira AR, Aquino-Junior J, Abbasi A, et al. Effects of aerobic exercise on molecular aspects of asthma: involvement of SOCS-JAK-STAT. Exerc Immunol Rev. 2019;25:50-62.

Zhao CY, Wang W, Yao HC, Wang X. SOCS3 is upregulated and targeted by miR30a-5p in allergic rhinitis. Int Arch Allergy Immunol. 2018;175(4):209-219.

Ozaki A, Seki Y, Fukushima A, Kubo M. The control of allergic conjunctivitis by suppressor of cytokine signaling (SOCS)3 and SOCS5 in a murine model. J Immunol. 2005;175(8):5489-5497.

Paul B, Mishra V, Chaudhury B, et al. Status of Stat3 in an ovalbumin-induced mouse model of asthma: analysis of the role of Socs3 and IL-6. Int Arch Allergy Immunol. 2009;148(2):99-108.

Horiuchi Y, Bae SJ, Katayama I. Overexpression of the suppressor of cytokine signalling 3 (SOCS3) in severe atopic dermatitis. Clin Exp Dermatol. 2006;31(1):100-104.

Ekelund E, Saaf A, Tengvall-Linder M, et al. Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis. Am J Hum Genet. 2006;78(6):1060-1065.

Seki Y, Inoue H, Nagata N, et al. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003;9(8):1047-1054.

Arakawa S, Hatano Y, Katagiri K. Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis. Clin Exp Immunol. 2004;135(3):505-510.

Kim TH, Kim K, Park SJ, et al. Expression of SOCS1 and SOCS3 is altered in the nasal mucosa of patients with mild and moderate/severe persistent allergic rhinitis. Int Arch Allergy Immunol. 2012;158(4):387-396.

Verma M, Chattopadhyay BD, Kumar S, Kumar K, Verma D. DNA methyltransferase 1(DNMT1) induced the expression of suppressors of cytokine signaling3 (Socs3) in a mouse model of asthma. Mol Biol Rep. 2014;41(7):4413-4424.

López E, Zafra MP, Sastre B, et al. Suppressors of cytokine signaling 3 expression in eosinophils: regulation by PGE₂ and Th2 cytokines. Clin Dev Immunol. 2011;2011:917015.

Chen Z, Wang S, Erekosima N, et al. IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling. J Allergy Clin Immunol. 2013;132(4):912-921.e5.

Moriwaki A, Inoue H, Nakano T, et al. T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma. Am J Respir Cell Mol Biol. 2011;44(4):448-455.

Zafra MP, Mazzeo C, Gámez C, et al. Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice. PloS One. 2014;9(3):e91996.

Inoue H, Fukuyama S, Matsumoto K, Kubo M, Yoshimura A. Role of endogenous inhibitors of cytokine signaling in allergic asthma. Curr Med Chem. 2007;14(2):181-189.

Böttcher I, Bellinghausen I, König B, Knop J, Saloga J. Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus contact allergens. Immunology. 2008;123(1):139-144.

Xu K, Wu N, Min Z, et al. Adoptive transfer of bone marrow-derived dendritic cells (BMDCs) alleviates OVA-induced allergic airway inflammation in asthmatic mice. Sci Rep. 2020;10(1):13915.

McGee HS, Stallworth AL, Agrawal T, Shao Z, Lorence L, Agrawal DK. Fms-like tyrosine kinase 3 ligand decreases T helper type 17 cells and suppressors of cytokine signaling proteins in the lung of house dust mite-sensitized and -challenged mice. Am J Respir Cell Mol Biol. 2010;43(5):520-529.

Zafra MP, Cañas JA, Mazzeo C, et al. SOCS3 silencing attenuates eosinophil functions in asthma patients. Int J Mol Sci. 2015;16(3):5434-5451.

Übel C, Graser A, Koch S, et al. Role of Tyk-2 in Th9 and Th17 cells in allergic asthma. Sci Rep. 2014;4:5865.

Draijer C, Speth JM, Penke LRK, et al. Resident alveolar macrophage-derived vesicular SOCS3 dampens allergic airway inflammation. FASEB J. 2020;34(3):4718-4731.

Sun W, Xiao B, Jia A, et al. MBD2-mediated Th17 differentiation in severe asthma is associated with impaired SOCS3 expression. Exp Cell Res. 2018;371(1):196-204.

Gao Y, Zhao H, Wang P, Wang J, Zou L. The roles of SOCS3 and STAT3 in bacterial infection and inflammatory diseases. Scand J Immunol. 2018;88(6):e12727.

Santana FPR, da Silva RC, Grecco SDS, et al. Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin attenuated chronic allergic airway inflammation in mice. Mediators Inflamm. 2019;2019:1356356.

Desai A, Jung MY, Olivera A, et al. IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3. J Allergy Clin Immunol. 2016;137(6):1863-1871.e6.

Traum D, Timothee P, Silver J, Rose-John S, Ernst M, LaRosa DF. IL-10-induced gp130 expression in mouse mast cells permits IL-6 trans-signaling. J Leukoc Biol. 2012;91(3):427-435.

Uto-Konomi A, Miyauchi K, Ozaki N, et al. Dysregulation of suppressor of cytokine signaling 3 in keratinocytes causes skin inflammation mediated by interleukin-20 receptor-related cytokines. PloS One. 2012;7(7):e40343.

Gallagher G, Eskdale J, Jordan W, et al. Human interleukin-19 and its receptor: a potential role in the induction of Th2 responses. Int Immunopharmacol. 2004;4(5):615-626.

Leigh T, Scalia RG, Autieri MV. Resolution of inflammation in immune and nonimmune cells by interleukin-19. Am J Physiol Cell Physiol. 2020;319(3):C457-C464.

Liao SC, Cheng YC, Wang YC, et al. IL-19 induced Th2 cytokines and was up-regulated in asthma patients. J Immunol. 2004;173(11):6712-6718.

Knosp CA, Carroll HP, Elliott J, et al. SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses. J Exp Med. 2011;208(7):1523-1531.

Knosp CA, Schiering C, Spence S, et al. Regulation of Foxp3+ inducible regulatory T cell stability by SOCS2. J Immunol. 2013;190(7):3235-3245.

Posselt G, Schwarz H, Duschl A, Horejs-Hoeck J. Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced activation in human monocyte-derived dendritic cells. J Immunol. 2011;187(6):2875-2884.

Lear TB, McKelvey AC, Evankovich JW, et al. KIAA0317 regulates pulmonary inflammation through SOCS2 degradation. JCI Insight. 2019;4(19):e129110.

Seki Y, Hayashi K, Matsumoto A, et al. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci USA. 2002;99(20):13003-13008.

Kubo M, Ozaki A, Tanaka S, Okamoto M, Fukushima A. Role of suppressor of cytokine signaling in ocular allergy. Curr Opin Allergy Clin Immunol. 2006;6(5):361-366.

Palmer DC, Guittard GC, Franco Z, et al. Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance. J Exp Med. 2015;212(12):2095-2113.

Zhu H, Blum RH, Bernareggi D, et al. Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes In vivo persistence and enhances anti-tumor activity. Cell Stem Cell. 2020;27(2):224-237.e6.

Yang XO, Zhang H, Kim BS, et al. The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation. Nat Immunol. 2013;14(7):732-740.

Takeshima H, Horie M, Mikami Y, et al. CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts. Allergol Int. 2019;68(1):101-109.

Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-233.

Ozdemir C, Kucuksezer UC, Akdis M, Akdis CA. The concepts of asthma endotypes and phenotypes to guide current and novel treatment strategies. Expert Rev Respir Med. 2018;12(9):733-743.

Ray A, Das J, Wenzel SE. Determining asthma endotypes and outcomes: complementing existing clinical practice with modern machine learning. Cell Rep Med. 2022;3(12):100857.

Chen Y, Liu W, Sun T, et al. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. J Immunol. 2013;190(7):3687-3695.

Jafarzadeh A, Naseri A, Shojaie L, et al. MicroRNA-155 and antiviral immune responses. Int Immunopharmacol. 2021;101(Pt A):108188.

Yin N, Xiong Y, Tao W, Chen J, Wang Z. Sinomenine alleviates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. Immunopharmacol Immunotoxicol. 2020;42(2):147-155.

Kang NJ, Han SC, Kang GJ, et al. Diphlorethohydroxycarmalol inhibits interleukin-6 production by regulating NF-κB, STAT5 and SOCS1 in lipopolysaccharide-stimulated RAW264.7 cells. Mar Drugs. 2015;13(4):2141-2157.

Suzuki T, Arakawa H, Mizuno T, et al. Differential regulation of eotaxin expression by dexamethasone in normal human lung fibroblasts. Am J Respir Cell Mol Biol. 2008;38(6):707-714.

Galam L, Parthasarathy PT, Cho Y, et al. Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection against hyperoxic acute lung injury. Free Radic Biol Med. 2015;84:196-205.

Yang C, Zheng C, Lin H, Li J, Zhao K. Role of suppressor of cytokine signaling 3 in the immune modulation of mesenchymal stromal cells. Inflammation. 2016;39(1):257-268.

Lin X, Lv J, Ge D, Bai H, Yang Y, Wu J. Heme oxygenase-1 alleviates eosinophilic inflammation by inhibiting STAT3-SOCS3 signaling. Pediatr Pulmonol. 2020;55(6):1440-1447.

Santana FPR, da Silva RC, Ponci V, et al. Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways. Biochem Pharmacol. 2020;180:114175.

Sun D, Wang J, Yang N, Ma H. Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice. Biochem Biophys Res Commun. 2016;477(1):83-90.

Liu J, Cheng Y, Zhang X, et al. Astragalin attenuates allergic inflammation in a murine asthma model. Inflammation. 2015;38(5):2007-2016.

López E, Zafra MP, Sastre B, Gámez C, Lahoz C, del Pozo V. Gene expression profiling in lungs of chronic asthmatic mice treated with galectin-3: downregulation of inflammatory and regulatory genes. Mediators Inflamm. 2011;2011:823279.

Park JH, Kim JW, Lee CM, et al. Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma. BMB Rep. 2012;45(5):311-316.

Hausding M, Tepe M, Ubel C, et al. Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma. Int Immunol. 2011;23(1):1-15.

Horiuchi Y, Bae S, Katayama I, Oshikawa T, Okamoto M, Sato M. Lipoteichoic acid-related molecule derived from the streptococcal preparation, OK-432, which suppresses atopic dermatitis-like lesions in NC/Nga mice. Arch Dermatol Res. 2006;298(4):163-173.

Yao R, Ma YL, Liang W, et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PloS One. 2012;7(10):e46082.

Luo W, Hu J, Xu W, Dong J. Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma. Front Immunol. 2022;13:974066.