Whereas atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, IL-17-producing Th (Th17) cells are also activated in AD lesional skin.
Our results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4⁺IL17⁺/CD4⁺FOXP3⁺ regulatory T cells and ILC3s.
Recent data support the theory of the involvement of IL-17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases).
Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-induced skin inflammation, are not well understood.
Furthermore, the therapeutic effect of anti-IL-4 receptor α against AD was not as high as that of IL-17 blockage against psoriasis, which implies a modification of the disease spectrum by non-Th2-type cytokine axes in AD.
Psoriasis is a disease largely driven by Th17 T-cells and associated IL-17 activation, while AD has a strong Th2 component associated with IL-4 and IL-13 over-production, and both diseases have activation of Th22 T-cells and Th1 pathways with increased IL-22 and IFNγ production, respectively.
Interleukin-19 (IL-19), a pro-inflammatory cytokine known to stimulate the production of T helper type 2 (Th2) cytokines, is induced by IL-17A and highly expressed in the lesional skin of psoriasis and atopic dermatitis (AD).
In addition, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑4, IL‑13, IL‑31 and IL‑17A was reduced in ear skin following AXE administration in AD mice.
AD-MSCs showed an upregulation of many Th1/Th17 cytokines [interleukin (IL)-6, IL-8, IL-12, IL-13, IL-17A, IL-17F, transforming growth factor-β, interferon-γ], while Th2 chemokines (IL-2, IL-4, IL-5, IL-23A) were downregulated in AD-MSCs.
Significant correlations between TLR2(+) (but not TLR4(+)) PB monocytes and the objective Scoring Atopic Dermatitis index (r = 0.604, p < 0.001), serum levels of IL-17a and TLR2(+) PB monocytes (r = 0.416, p = 0.027), and IL-4 and TLR2(+) PB monocytes (r = -0.307, p = 0.014) were observed during AD exacerbation.
The study did not establish any links between the IL-23R and IL-17A gene SNPs and the likelihood of developing AD resulting from gene-gene interaction.
IL-25, an IL-17 family cytokine, was recently reported to induce TH2-type immune responses and to contribute to several allergic diseases, such as atopic dermatitis and asthma.
Positive correlations were found between miR-155 expression and AD severity, Th17 cell percentage, RORγt mRNA expression and IL-17 mRNA expression and plasma concentration, while negative correlations were observed between miR-155 expression and SOCS1 mRNA expression and plasma concentration in AD peripheral circulation and skin lesions.
In conclusion, our study provides evidence for a previously unrecognized protective role for EGF in AD and a new role for EGF in modulating IL-17 responses in the skin.
The modulation by LL-37 of the keratinocyte proinflammatory responses induced by cytokine milieus and dsRNA suggests novel roles for LL-37 in skin inflammation such as the promotion of IL17/IL-22/IL-6-associated psoriasis and suppression of TSLP-associated atopic dermatitis.
The percentage of CD4+/CD25high+/FOXP3+ Treg lymphocytes with expression of IL-17 was significantly higher in AD group than in healthy subjects (0.3% versus 0.06%; P=0.011).
In the skin lesions, IL-17(+) cells were more represented in psoriasis than in AD, while the number of IL-4-producing cells was reduced in psoriasis patients than in AD ones.
Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.