Abstract
The skin is a formidable physical barrier that protects the body from infection and other foreign irritants. Immune cells in the skin play a critical role in host defense, and include a number of specialized cell types such as keratinocytes, Langerhans cells, dendritic cells, and various subsets of T cells, which aid the body in fighting pathogens. However, when immune function in the skin is compromised, either due to a hereditary defect in skin barrier function, or as a result of unwarranted immune sensitization, these same cells can drive the development of skin disease and induce chronic cutaneous inflammation. In this chapter, we will review the immunological functions of the skin and discuss the roles of various immune cells and cellular mediators in host defense. Next, we will examine in detail the immunological basis and pathophysiology of two widely prevalent skin diseases mediated by immune cells, namely atopic dermatitis and psoriasis. The immunopathogenesis of these diseases will be discussed in light of current evidence from the literature and the roles of various subsets of helper T cells, including TH2, TH17, and TH22 cells will be highlighted. Lastly, we will examine the pharmacology of various immunotherapeutic drugs used in the treatment of these diseases. These include glucocorticoids, anti-proliferative agents, phosphodiesterase inhibitors, and various biologics such as inhibitors of IL-4, IL-13, IL-17, and IL-12 and IL-23. In the From Bench to Bedside section, we will review the discovery and development of Dupilumab for the treatment of atopic dermatitis.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSuggested Reading
AbuHilal M, Walsh S, Shear N. The role of IL-17 in the pathogenesis of psoriasis and update on IL-17 inhibitors for the treatment of plaque psoriasis. J Cutan Med Surg. 2016;20:509–16.
Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol. 2007;8:942–9.
Akdis CA, Akdis M. Immunological differences between intrinsic and extrinsic types of atopic dermatitis. Clin Exp Allergy. 2003;33:1618–21.
Akdis CA, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL consensus report. Allergy. 2006;61:969–87.
Amano W, et al. The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J Allergy Clin Immunol. 2015;136:667–77.e667.
Armstrong AW, et al. Effect of ixekizumab treatment on work productivity for patients with moderate-to-severe plaque psoriasis: analysis of results from 3 randomized phase 3 clinical trials. JAMA Dermatol. 2016;152:661–9.
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2:e24137.
Beck LA, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–9.
Bissonnette R, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175:902–11.
Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018;55:379–90.
Blauvelt A, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol. 2017;76:60–9.e69.
Bonefeld CM, Geisler C. The role of innate lymphoid cells in healthy and inflamed skin. Immunol Lett. 2016;179:25–8.
Bruggen MC, et al. In situ mapping of innate lymphoid cells in human skin: evidence for remarkable differences between Normal and inflamed skin. J Invest Dermatol. 2016;136:2396–405.
Brunner PM, et al. A mild topical steroid leads to progressive anti-inflammatory effects in the skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2016;138:169–78.
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017a;139:S65–76.
Brunner PM, et al. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol. 2017b;137:18–25.
Brunner PM, et al. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations. J Allergy Clin Immunol. 2018;141:2094–106.
Castro M, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486–96.
Chalmers JR, et al. Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative). Br J Dermatol. 2018;178:e332–41.
Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987;166:1229–44.
Coffman RL. Converging discoveries: the first reports of IL-4. J Immunol. 2013;190:847–8.
Cole C, et al. Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis. J Allergy Clin Immunol. 2014;134:82–91.
Czarnowicki T, Krueger JG, Guttman-Yassky E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract. 2014;2:371–9;. quiz 380-371.
Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol. 2017;139:1723–34.
Davis DM, Borok J, Udkoff J, Lio P, Spergel J. Atopic dermatitis: phototherapy and systemic therapy. Semin Cutan Med Surg. 2017;36:118–23.
Dong J, Goldenberg G. New biologics in psoriasis: an update on IL-23 and IL-17 inhibitors. Cutis. 2017;99:123–7.
Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol. 2009;10:857–63.
Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016;138:350–8.e351.
Egeberg A. Phase 3 trials of Ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:2101–2.
Eichenfield LF, Stein Gold LF. Systemic therapy of atopic dermatitis: welcome to the revolution. Semin Cutan Med Surg. 2017;36:S103–5.
Eichenfield LF, et al. Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis. J Am Acad Dermatol. 2017;77:641–9.e645.
Esaki H, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol. 2016;138:1639–51.
Eyerich K, et al. IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol. 2009a;123:59–66.e54.
Eyerich S, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest. 2009b;119:3573–85.
Eyerich S, et al. Mutual antagonism of T cells causing psoriasis and atopic eczema. N Engl J Med. 2011;365:231–8.
Eyerich K, Dimartino V, Cavani A. IL-17 and IL-22 in immunity: driving protection and pathology. Eur J Immunol. 2017;47:607–14.
Furue M, Kadono T. “Inflammatory skin march” in atopic dermatitis and psoriasis. Inflamm Res. 2017;66:833–42.
Ganguly D, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206:1983–94.
Gisondi P, Girolomoni G. Apremilast in the therapy of moderate-to-severe chronic plaque psoriasis. Drug Des Devel Ther. 2016;10:1763–70.
Gittler JK, et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130:1344–54.
Glatzer F, et al. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol. 2013;132:1358–67.
Gordon KB, Colombel JF, Hardin DS. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016a;375:2102.
Gordon KB, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016b;375:345–56.
Gottlieb AB, et al. Efficacy, tolerability, and pharmacodynamics of apremilast in recalcitrant plaque psoriasis: a phase II open-label study. J Drugs Dermatol. 2013;12:888–97.
Griffin GK, et al. IL-17 and TNF-alpha sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation. J Immunol. 2012;188:6287–99.
Grunig G, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261–3.
Gutowska-Owsiak D, et al. IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol. 2012;21:104–10.
Guttman-Yassky E, Krueger JG, Lebwohl MG. Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment. Exp Dermatol. 2018;27:409–17.
Halim TY, et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity. 2014;40:425–35.
Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994;94:870–6.
Hamilton JD, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014;134:1293–300.
Hanifin JM, Reed ML, Eczema P, Impact Working G. A population-based survey of eczema prevalence in the United States. Dermatitis. 2007;18:82–91.
He JQ, et al. Genetic variants of the IL13 and IL4 genes and atopic diseases in at-risk children. Genes Immun. 2003;4:385–9.
Hijnen DJ, ten Berge O, Timmer-de Mik L, Bruijnzeel-Koomen CA, de Bruin-Weller MS. Efficacy and safety of long-term treatment with cyclosporin A for atopic dermatitis. J Eur Acad Dermatol Venereol. 2007;21:85–9.
Howard M, et al. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982;155:914–23.
Howell MD, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124:R7–R12.
Howell MD, Parker ML, Mustelin T, Ranade K. Past, present, and future for biologic intervention in atopic dermatitis. Allergy. 2015;70:887–96.
Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365:1315–27.
Isakson PC, Pure E, Vitetta ES, Krammer PH. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982;155:734–48.
Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity. 2011;34:149–62.
Iwasaki M, et al. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. J Invest Dermatol. 2002;119:609–16.
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522–5.
Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–83.
Khattri S, et al. Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology. J Allergy Clin Immunol. 2014;133:1626–34.
Khattri S, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26:28–35.
Kim BS, et al. TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci Transl Med. 2013;5:170ra116.
Kim J, et al. Epidermal thymic stromal lymphopoietin predicts the development of atopic dermatitis during infancy. J Allergy Clin Immunol. 2016;137:1282–5.e1284.
Kopp T, et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature. 2015;521:222–6.
Kupetsky EA, Mathers AR, Ferris LK. Anti-cytokine therapy in the treatment of psoriasis. Cytokine. 2013;61:704–12.
Lande R, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449:564–9.
Lande R, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621.
Langley RG, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326–38.
Lebwohl M, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318–28.
Lee F, et al. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986;83:2061–5.
Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134:769–79.
Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015;73:395–9.
Lopez-Ferrer A, Vilarrasa E, Gich IJ, Puig L. Adalimumab for the treatment of psoriasis in real life: a retrospective cohort of 119 patients at a single Spanish centre. Br J Dermatol. 2013;169:1141–7.
Lopez-Ferrer A, Vilarrasa E, Puig L. Secukinumab (AIN457) for the treatment of psoriasis. Expert Rev Clin Immunol. 2015;11:1177–88.
Margolis DJ, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol. 2012;130:912–7.
McAleer MA, Irvine AD. The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol. 2013;131:280–91.
McKenzie AN, et al. Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci U S A. 1993;90:3735–9.
Mease PJ, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329–39.
Mease PJ, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76:79–87.
Mennini M, Dahdah L, Fiocchi A. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2017;376:1090.
Menter A, et al. Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate-to-severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2 and UNCOVER-3). J Eur Acad Dermatol Venereol. 2017;31:1686–92.
Minty A, et al. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature. 1993;362:248–50.
Montaldo E, Juelke K, Romagnani C. Group 3 innate lymphoid cells (ILC3s): origin, differentiation, and plasticity in humans and mice. Eur J Immunol. 2015;45:2171–82.
Moreno AS, McPhee R, Arruda LK, Howell MD. Targeting the T helper 2 inflammatory axis in atopic dermatitis. Int Arch Allergy Immunol. 2016;171:71–80.
Morgan JG, Dolganov GM, Robbins SE, Hinton LM, Lovett M. The selective isolation of novel cDNAs encoded by the regions surrounding the human interleukin 4 and 5 genes. Nucleic Acids Res. 1992;20:5173–9.
Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984;81:6851–5.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.
Nakajima S, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol. 2012;129:1048–1055 e1046.
Nast A, Jacobs A, Rosumeck S, Werner RN. Efficacy and safety of systemic long-term treatments for moderate-to-severe psoriasis: a systematic review and meta-analysis. J Invest Dermatol. 2015;135:2641–8.
Nemoto O, et al. The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2016;174:296–304.
Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361:496–509.
Niebuhr M, Scharonow H, Gathmann M, Mamerow D, Werfel T. Staphylococcal exotoxins are strong inducers of IL-22: a potential role in atopic dermatitis. J Allergy Clin Immunol. 2010;126:1176–83.e1174.
Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015a;135:324–36.
Noda S, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015b;136:1254–64.
Nograles KE, et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008;159:1092–102.
Nograles KE, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123:1244–52.e1242.
Noma Y, et al. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature. 1986;319:640–6.
Nomura I, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171:3262–9.
Oldhoff JM, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005;60:693–6.
Oliva M, Renert-Yuval Y, Guttman-Yassky E. The ‘omics’ revolution: redefining the understanding and treatment of allergic skin diseases. Curr Opin Allergy Clin Immunol. 2016;16:469–76.
Ong PY, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347:1151–60.
Oppmann B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25.
Paller AS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75:494–503.e496.
Papp KA, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273–86.
Parham C, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168:5699–708.
Perez-Aso M, et al. Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther. 2015;17:249.
Pincelli C, Schafer PH, French LE, Augustin M, Krueger JG. Mechanisms underlying the clinical effects of apremilast for psoriasis. J Drugs Dermatol. 2018;17:835–40.
Puig L, Lopez A, Vilarrasa E, Garcia I. Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials with different time points. J Eur Acad Dermatol Venereol. 2014;28:1633–53.
Rabenhorst A, Hartmann K. Interleukin-31: a novel diagnostic marker of allergic diseases. Curr Allergy Asthma Rep. 2014;14:423.
Robinson DS, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298–304.
Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012;148:890–7.
Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583–90.
Schafer PH, et al. Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal. 2014;26:2016–29.
Schafer PH, Chen P, Fang L, Wang A, Chopra R. The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1). J Immunol Res. 2015;2015:906349.
Schafer PH, et al. Phosphodiesterase 4 in inflammatory diseases: effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28:753–63.
Schurich A, Raine C, Morris V, Ciurtin C. The role of IL-12/23 in T cell-related chronic inflammation: implications of immunodeficiency and therapeutic blockade. Rheumatology (Oxford). 2018;57:246–54.
Sehra S, et al. IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation. J Immunol. 2010;184:3186–90.
Silverberg JI. Persistence of childhood eczema into adulthood. JAMA Dermatol. 2014;150:591–2.
Silverberg JI. Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies. Allergy. 2015;70:1300–8.
Silverberg JI, Simpson EL. Associations of childhood eczema severity: a US population-based study. Dermatitis. 2014;25:107–14.
Simon D. Systemic therapy of atopic dermatitis in children and adults. Curr Probl Dermatol. 2011;41:156–64.
Simon D, Bieber T. Systemic therapy for atopic dermatitis. Allergy. 2014;69:46–55.
Simpson EL, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335–48.
Simpson EL, Akinlade B, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2017a;376:1090–1.
Simpson EL, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017b;77:623–33.
Slater NA, Morrell DS. Systemic therapy of childhood atopic dermatitis. Clin Dermatol. 2015;33:289–99.
Sofen H, et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014;133:1032–40.
Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. 2011;12:383–90.
Spertino J, Lopez-Ferrer A, Vilarrasa E, Puig L. Long-term study of infliximab for psoriasis in daily practice: drug survival depends on combined treatment, obesity and infusion reactions. J Eur Acad Dermatol Venereol. 2014;28:1514–21.
Suarez-Farinas M, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132:361–70.
Thaci D, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387:40–52.
Torres T, Romanelli M, Chiricozzi A. A revolutionary therapeutic approach for psoriasis: bispecific biological agents. Expert Opin Investig Drugs. 2016;25:751–4.
Ulven T, Kostenis E. Novel CRTH2 antagonists: a review of patents from 2006 to 2009. Expert Opin Ther Pat. 2010;20:1505–30.
van de Kerkhof PC, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75:83–98.e84.
Veilleux MS, Shear NH. Biologics in patients with skin diseases. J Allergy Clin Immunol. 2017;139:1423–30.
Vena GA, Vestita M, Cassano N. Psoriasis and cardiovascular disease. Dermatol Ther. 2010;23:144–51.
Vilarrasa E, et al. ORBIT (outcome and retention rate of biologic treatments for psoriasis): a retrospective observational study on biologic drug survival in daily practice. J Am Acad Dermatol. 2016;74:1066–72.
Volf EM, Au SC, Dumont N, Scheinman P, Gottlieb AB. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol. 2012;11:341–6.
Walker C, et al. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis. 1992;146:109–15.
Wang YH, Liu YJ. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy. 2009;39:798–806.
Welsch K, Holstein J, Laurence A, Ghoreschi K. Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors. Eur J Immunol. 2017;47:1096–107.
Werfel T, Biedermann T. Current novel approaches in systemic therapy of atopic dermatitis: specific inhibition of cutaneous Th2 polarized inflammation and itch. Curr Opin Allergy Clin Immunol. 2015;15:446–52.
Werfel T, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138:336–49.
Wills-Karp M, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.
Wolk K, et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol. 2006;36:1309–23.
Wollenberg A, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019;143:135–41.
Yiu ZZ, Warren RB. Novel Oral therapies for psoriasis and psoriatic arthritis. Am J Clin Dermatol. 2016;17:191–200.
Zheng T, et al. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009;129:742–51.
Ziegler SF, Liu YJ. Thymic stromal lymphopoietin in normal and pathogenic T cell development and function. Nat Immunol. 2006;7:709–14.
Zurawski SM, Vega F Jr, Huyghe B, Zurawski G. Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J. 1993;12:2663–70.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Mathias, C.B. (2020). Inflammation of the Skin and Its Therapeutic Targets. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_5
Download citation
DOI: https://doi.org/10.1007/978-3-030-19922-7_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-19921-0
Online ISBN: 978-3-030-19922-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)