Atopic dermatitis
AD is a complex chronic inflammatory skin disease that is associated
with skin barrier defects and the activation of immune responses in the
skin by environmental allergens and/or intrinsic
factors.30 Although
type 2 inflammatory responses and elevated IgE are known as the main
characteristics of AD, some patients actually develop stronger T helper
cell (Th) Th17/Th22
responses31. Among
other characteristic features, activation of keratinocytes with some
similarities to another inflammatory skin disease, psoriasis, plays an
important role in
AD30,32.
Research on miRNAs in AD started with an array analysis of lesional skin
samples from AD and psoriasis patients. The results of this early study
suggested that alterations in miRNA levels in the skin of AD patients
partially overlapped with that of psoriatic skin and include multiple
miRNAs shown to be modulated in other inflammatory
conditions33. For
example, miR-21 and miR-146a were shown to be upregulated in the skin of
psoriasis and AD
patients33, of which
miR-21 function in airway inflammation is discussed in other sections of
this review. miR-146a was demonstrated to inhibit many pro-inflammatory
chemokines in keratinocytes through targeting multiple factors of the
NFκ-B pathway34-37 and
miR-146a-deficient mice developed stronger inflammation in both AD and
psoriasis
models36,38.
On the other hand, it has been shown that miR-146a deficiency in mice
leads to a defect in IgE
production39,40and is linked to a type 1/type 17 skewing
phenotype41. However,
as a negative relationship between miR-146a and IgE levels in patient
serum samples was
detected39. It appears
that miR‐146a is needed for the production of IgE and suppression of
type 1/17‐cell‐mediated immune responses in mice. Therefore, the
increased expression of miR‐146a in the case of allergic inflammation
might have limited influence on type‐2 cell‐mediated immune responses in
a subgroup of AD patients with increased IgE.
Another miRNA that may influence the development of AD through its
function in the immune system is miR-155. It was shown that miR-155 is
overexpressed in the skin of AD patients, most likely due to
infiltrating immune cells, and suggested that miR-155 may influence the
development of AD through the downregulation of cytotoxic T
lymphocyte-associated antigen 4 (CTLA4), a negative regulator of T cell
activation37. In
addition, it was reported that miR-155 expression positively correlated
with AD severity, the number of Th17 cells and IL-17 mRNA expression and
plasma concentration, indicating that miR-155 may influence the
pathogenesis of AD through its effect on differentiation and function of
Th17 cells42. The
expression changes and effects in cell cultures of other miRNAs,
including miR-151a43,
-143, -124 and 10a are reported and outlined in Table 1 .
Altogether, the studies of miRNAs in AD clearly demonstrate that miRNAs
affect the severity of skin inflammation, modulate cellular responses of
keratinocytes and specialized immune cells and thereby influence the
pathogenesis of AD.