Targeting IL-4 for the Treatment of Atopic Dermatitis

Overview

Journal Immunotargets Ther

Publisher Dove Medical Press

Specialty Allergy & Immunology

Date 2020 Oct 16

PMID 33062619

Citations 42

Authors

Andrea Chiricozzi

Martina Maurelli

Ketty Peris

Giampiero Girolomoni

Affiliations

Soon will be listed here.

Abstract

Atopic dermatitis (AD) is an immune-mediated inflammatory skin disease characterized by a predominant type 2 immune response. Type 2 immunity is driven by multiple cytokines, including interleukin (IL)‑4 and IL-13 that are considered central to AD pathogenesis and key therapeutic targets. The dual inhibition of these two cytokines or the selective inhibition of IL-13 proved elevated efficacy in treating AD, whereas the selective inhibition of IL-4 has been poorly investigated as IL-4 inhibiting agents did not show any advance in clinical development programs. This review describes the pathogenic role of IL-4 in AD and briefly resumes the main features of compounds selectively blocking IL-4.

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References

Nomura I, Goleva E, Howell M, Hamid Q, Ong P, Hall C . Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003; 171(6):3262-9. DOI: 10.4049/jimmunol.171.6.3262. View

Kim B, Leung D, Boguniewicz M, Howell M . Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008; 126(3):332-7. PMC: 2275206. DOI: 10.1016/j.clim.2007.11.006. View

Simpson E, Bieber T, Guttman-Yassky E, Beck L, Blauvelt A, Cork M . Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2016; 375(24):2335-2348. DOI: 10.1056/NEJMoa1610020. View

Cho S, Strickland I, Boguniewicz M, Leung D . Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. J Allergy Clin Immunol. 2001; 108(2):269-74. DOI: 10.1067/mai.2001.117455. View

Werfel T, Allam J, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E . Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016; 138(2):336-49. DOI: 10.1016/j.jaci.2016.06.010. View

Ong P, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T . Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002; 347(15):1151-60. DOI: 10.1056/NEJMoa021481. View

Sehra S, Yao Y, Howell M, Nguyen E, Kansas G, Leung D . IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation. J Immunol. 2010; 184(6):3186-90. PMC: 2837507. DOI: 10.4049/jimmunol.0901860. View

Berdyshev E, Goleva E, Bronova I, Dyjack N, Rios C, Jung J . Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018; 3(4). PMC: 5916244. DOI: 10.1172/jci.insight.98006. View

Kim J, Jung K, Kim J, Kim S, Park H, Kim Y . Engineering of anti-human interleukin-4 receptor alpha antibodies with potent antagonistic activity. Sci Rep. 2019; 9(1):7772. PMC: 6533264. DOI: 10.1038/s41598-019-44253-9. View

10.

Nishi N, Yamamoto S, Ou W, Muro E, Inada Y, Hamasaki Y . Enhanced CCL26 production by IL-4 through IFN-gamma-induced upregulation of type 1 IL-4 receptor in keratinocytes. Biochem Biophys Res Commun. 2008; 376(1):234-40. DOI: 10.1016/j.bbrc.2008.08.136. View

11.

Howell M, Kim B, Gao P, Grant A, Boguniewicz M, DeBenedetto A . Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007; 120(1):150-5. PMC: 2669594. DOI: 10.1016/j.jaci.2007.04.031. View

12.

He R, Kim H, Yoon J, Oyoshi M, MacGinnitie A, Goya S . Exaggerated IL-17 response to epicutaneous sensitization mediates airway inflammation in the absence of IL-4 and IL-13. J Allergy Clin Immunol. 2009; 124(4):761-70.e1. PMC: 2895457. DOI: 10.1016/j.jaci.2009.07.040. View

13.

Okazaki H, Kakurai M, Hirata D, Sato H, Kamimura T, Onai N . Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C-C chemokine receptor 4 in atopic dermatitis. Clin Exp Allergy. 2002; 32(8):1236-42. DOI: 10.1046/j.1365-2745.2002.01383.x. View

14.

Newcomb D, Boswell M, Zhou W, Huckabee M, Goleniewska K, Sevin C . Human TH17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production. J Allergy Clin Immunol. 2011; 127(4):1006-13.e1-4. PMC: 3916096. DOI: 10.1016/j.jaci.2010.11.043. View

15.

Pelly V, Kannan Y, Coomes S, Entwistle L, Ruckerl D, Seddon B . IL-4-producing ILC2s are required for the differentiation of T2 cells following Heligmosomoides polygyrus infection. Mucosal Immunol. 2016; 9(6):1407-1417. PMC: 5257265. DOI: 10.1038/mi.2016.4. View

16.

Miake S, Tsuji G, Takemura M, Hashimoto-Hachiya A, Vu Y, Furue M . IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis. Int J Mol Sci. 2019; 20(16). PMC: 6719908. DOI: 10.3390/ijms20164053. View

17.

Pene J, Rousset F, Briere F, Chretien I, Bonnefoy J, Spits H . IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988; 85(18):6880-4. PMC: 282082. DOI: 10.1073/pnas.85.18.6880. View

18.

Werfel T . The role of leukocytes, keratinocytes, and allergen-specific IgE in the development of atopic dermatitis. J Invest Dermatol. 2009; 129(8):1878-91. DOI: 10.1038/jid.2009.71. View

19.

Bhogal R, Bona C . Regulatory effect of extracellular signal-regulated kinases (ERK) on type I collagen synthesis in human dermal fibroblasts stimulated by IL-4 and IL-13. Int Rev Immunol. 2008; 27(6):472-96. DOI: 10.1080/08830180802430974. View

20.

Howell M, Fairchild H, Kim B, Bin L, Boguniewicz M, Redzic J . Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. J Invest Dermatol. 2008; 128(9):2248-58. DOI: 10.1038/jid.2008.74. View