CCL18
C-C motif chemokine 18 precursor (Alternative macrophage activation-associated CC chemokine 1) (AMAC-1) (CC chemokine PARC) (Dendritic cell chemokine 1) (DC-CK1) (Macrophage inflammatory protein 4) (MIP-4) (Pulmonary and activation-regulated chemokine) (Small-inducible cytokine A18) [Contains: CCL18(1-68); CCL18(3-69); CCL18(4-69)] [AMAC1] [DCCK1] [MIP4] [PARC] [SCYA18]
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Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. We sought to characterize age-related changes in the AD profile. We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b and FcεRI , P < .05) decreased with age. T 2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T 2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T 22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T 1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T 17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T 2 downregulation (CCL26; r = -0.32, P < .1) and T 1 upregulation (IFN-γ; r = 0.48, P < .01) with age. The adult AD profile varies with age. Although T 1/T 17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T 2/T 22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cytokines
- Dermatitis, Atopic
- Female
- Gene Expression
- Humans
- Male
- Middle Aged
- Phenotype
- Severity of Illness Index
- Skin
- Young Adult
Keywords
- Atopic dermatitis
- T(H)1
- T(H)17
- T(H)2
- T(H)22
- aging
- biomarker
- filaggrin
- hyperplasia
- loricrin
- skin