Journal of Dermatological Science 97 (2020) 2–8

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Journal of Dermatological Science

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Invited Review Article

The role of ceramides in skin homeostasis and inflammatory

skin diseases
Qingyang Li, Hui Fang, Erle Dang, Gang Wang*
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

A R T I C L E I N F O A B S T R A C T

Article history: Ceramides, members of sphingolipid family, are not only the building blocks of epidermal barrier
Received 26 November 2019 structure, but also bioactive metabolites involved in epidermal self-renewal and immune regulation.
Accepted 2 December 2019 Hence, abnormal ceramide expression profile is recognized to defect extracellular lipid organization,
disturb epidermal self-renewal, exacerbate skin immune response and actively participate in progression
Keywords: of several inflammatory dermatoses, exemplifying by psoriasis and atopic dermatitis. Here, we discuss
Ceramides recent advances in understanding skin ceramides and their regulatory roles in skin homeostasis and
Epidermal barrier
pathogenic roles of altered ceramide metabolism in inflammatory skin diseases. These insights provide
Inflammatory dermatoses
Psoriasis
new opportunities for therapeutic intervention in inflammatory dermatoses.
Atopic dermatitis © 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

1. Introduction progression of inflammatory skin diseases that may provide a

Epidermal barrier, which mainly refers to the stratum
corneum (SC), creates a first-line defense against myriad
potentially harmful invaders, diminishes transepidermal water
loss (TEWL), and plays an essential role in maintaining skin
homeostasis. Recognized as the "brick and mortar" model,
epidermal barrier is constructed of 15–25 layers of anucleated
corneocytes embedded in lamellar lipid matrix. Epidermal
ceramides account for approximately 50 % of total epidermal
lipid by weight. Along with free fatty acid and cholesterol,
ceramides constitute a hydrophilic extracellular lipid matrix,
which is indispensable for permeability barrier function [1]. In
addition, ceramides also act as an active second messenger,
regulate keratinocyte proliferation and differentiation, enhance
proinflammatory cytokines production, and modulate immune
responses. Aberrant metabolism and function of ceramides is
involved in the pathogenesis of several inflammatory skin
diseases, including psoriasis, atopic dermatitis (AD) and ichthyo-
sis. In this review, we focus on the role of ceramides in the
prospective for further depicting the pathogenesis and therapeu-
tic strategies of inflammatory dermatoses.
2. Expression and regulation of epidermal ceramide profile
Epidermal ceramides mainly reside in SC and exhibit great
molecular heterogeneity, comprising 18 classes. To discriminate
ceramide classes, a nomenclature is used, which is based on the
abbreviation of its fatty acid (N, non-hydroxy; A, α-hydroxy; O, v-
hydroxy; EO, esterified v- hydroxy) and sphingoid base (DS,
dihydrosphingosine; S, sphingosine; P, phytosphingosine; H, 6-
hydroxy-sphingosine; T, dihydroxy-sphinganine). These ceramide
classes each contain 300–1000 species based on their specific
combination of fatty acids and base groups [2]. The most abundant
ceramides in normal epidermis are Cer[NH], Cer[NP], Cer[AH] and
Cer[AP], while Cer[EODS], Cer[ADS] and Cer[EOP] are among the
least. In terms of their acyl chain length, ceramides are varied from
having long chain (LC) (C14–C18), very long chain (VLC) (C20–C26),
to ultra-long chain (ULC) (>C26). Acyl chain length in healthy skin

Abbreviations: acylCer, acylated ceramides; AD, atopic dermatitis; CXCL1, C-X-C motif chemokine ligand 1; CerS, ceramide synthase; CLE, corneocyte lipid envelope; DS,
dihydrosphingosine; T, dihydroxy-sphinganine; ELOVL, elongase of long-chain fatty acids; EO, esterified v- hydroxy; (IFN) -g, interferon; IL, interleukin; LC, long chain; LPP,
long periodicity phase; NMF, natural moisturizing factor; N, non-hydroxy; NLRP3, nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3; PPAR,
peroxisome proliferator-activated receptor; P, phytosphingosine; phytoCer, phytosphingosine-carrying ceramides; PASI, Psoriasis Area Severity Index; SCORAD, Severity
Scoring of Atopic Dermatitis; SM, sphingomyelin; S, sphingosine; S1P, sphingosine-1-phosphate; SC, stratum corneum; TLR, toll-like receptor; TEWL, transepidermal water
loss; TRPA1, transient receptor potential ankyrin 1; TRPV1, transient receptor potential vanilloid 1; TNF, tumor necrosis factor; ULC, ultra-long chain; UV, ultraviolet; VLC, very
long chain; A, α-hydroxy; GlcCerase, β-glucocerebrosidase; O, v- hydroxy; H, 6-hydroxy-sphingosine.
* Corresponding author.
E-mail address: xjwgang@fmmu.edu.cn (G. Wang).

https://doi.org/10.1016/j.jdermsci.2019.12.002
0923-1811/ © 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8
mainly ranges from C16 to C36, mostly C24 [3]. Heterogeneity in
ceramides molecular architecture enables significant disparity of
ceramides functions among classes, suggesting their diverse roles
in skin homeostasis.
Epidermal ceramide expression profile is influenced by both
internal and external factors. During their de novo or salvage
synthesis, ceramides mainly requires a same set of enzymes,
except for ceramide synthases (CerSs), of which CerS3 is
demonstrated to be exclusively required for ULC ceramides.
Downregulating CerS3 activity leads to reduced proportion of
ULC ceramides. Besides, it was reported that ZAG, an adipokine,
could increase Cer[EOS], Cer[NP] and Cer[AS], and eventually
restore skin barrier function in AD mice [4]. SC ceramide
composition is altered by age. Children (<6 year-old) exhibit
relatively more Cer[NH], and less α-hydroxy and esterified v-
hydroxy ceramides than adults [5]. Cer[EOS] is significantly
reduced in seniors (>50 s) compared to younger individuals
(20
40 s). Moreover, the degree of fatty acid chain saturation of
Cer[EOS], which has marked effects on lamellar and lateral lipid
organization, is decreased in autumn and winter, partially
accounting for worse barrier function and higher reoccurrence
rate of psoriasis in winter [6]. Ultraviolet (UV) irradiation exposure
leads to an increase in ceramides and a decrease in sphingomyelin
(SM) in HaCaT cells, possibly through promoting ceramide salvage
pathway [7].Therefore, regulated by various factors, epidermal
ceramides keep in dynamic equilibrium and play critical roles in
skin homeostasis.
3. Ceramides – key regulators in maintaining skin homeostasis
3.1. Ceramides maintain epidermal barrier function
Ceramides, fatty acid and cholesterol constitute the extracel-
lular lipid matrix of epidermal barrier in an approximately
equimolar ratio and are assembled in a dense orthorhombic
lateral packing within SC interstices. Among them, ceramides are
central to the permeability barrier structure and function.
Replacing C24 Cer[NS] by C16 Cer[NS] in a SC lipid membrane
model augments hexagonal lateral packing, lipid membrane
destabilization and phase separation, which results in increased
permeability to water, theophylline and indomethacin [8].
Acylated ceramides (acylCer), such as Cer[EOS], covalently bind
to envoplakin and involucrin and form corneocyte lipid envelope
(CLE), which acts as a scaffold linking hydrophilic corneocytes and
lipophilic extracellular lipids [9]. AcylCer is required for the
formation of the long periodicity phase (LPP) and the ortho-
rhombic lateral packing of lipids, which are considered to be
essential in maintaining the skin lipid lamellae structure [10].
Reduced acylCer can lead to a "leaky" permeability barrier and
often exhibit xerotic and scaly appearance as seen in ichthyosis
and AD. Therefore, a balanced expression of ceramide classes is
required for stable and dense organization of SC lipids and a well-
functioning epidermal barrier.
3.2. Ceramides promote epidermal self-renewal
In addition, ceramides have been reported as an active
second messenger with pro-apoptosis function in several tissues
and cells. In skin, although in lack of direct evidence, ceramides
were speculated to regulate keratinocyte proliferation/differen-
tiation balance by exerting anti-proliferative and pro-apoptotic
effects. Ceramide synthesis is enhanced along with the rate of
keratinocyte differentiation both in vitro and in vivo [11].
Ceramides inhibit cell growth in human skin squamous cell
carcinoma and are involved in both death receptors- and
mitochondria-related apoptosis [12]. Interestingly, application of
3
stable ceramide analogs causes downregulation of selenoproteins
and glutathione peroxidase 4, which could promote ferroptosis
[13]. Although ceramides are indispensable in epidermis, exces-
sive ceramides may cause irreversible cell death and inflamma-
tion, as seen in UV-induced skin damage [14]. Hence, the
equilibrium between ceramide synthesis and degradation is
essential for maintaining epidermal renewal and normal homeo-
stasis.
3.3. Ceramides regulate skin immune response
Ceramides and their derivatives have been largely investigated
in their roles in modulating immune system and inflammation. By
promoting the stabilization of Toll-like receptor (TLR) 4,
ceramides were shown to enhance LPS-induced proinflammatory
signaling [15]. Studies in microglia have discovered that
ceramides function as intracellular modulators of nucleotide-
binding domain and leucine-rich-repeat-containing family pyrin
3 (NLRP3) inflammasome assembly and induce the secretion of
interleukin (IL) -1β [16]. Sphingosine-1-phosphate (S1P), a
ceramide metabolite, upregulates cathelicidin antimicrobial
peptide expression in keratinocytes and activates innate immu-
nity [17]. Thus, ceramides are regarded as bioactive transmitter
involved in various inflammatory signaling pathways. Further
studies need to focus on whether extracellular ceramides stacked
in the lipid matrix in SC also hold multifunctional properties in
inflammation and immune response.
4. Ceramides in inflammatory skin diseases
4.1. Psoriasis
Psoriasis is a T cell mediated inflammatory skin disease,
characterized by attenuated epidermal barrier function.
Koebner phenomenon and efficacy of occlusion in clinical
practice, offer eloquent examples of how psoriasis could be
provoked by disruption of epidermal permeability barrier.
Genome-wide association studies in both European and
Chinese populations have identified skin barrier regulatory
genes of the late cornified envelope as new susceptibility genes
for psoriasis [18]. Recently, our group has demonstrated that
disruption of epidermal barrier, by increasing mechanical
stress, could exacerbate psoriasis phenotype via inducing
keratinocyte proliferation and overexpression of C

X

C motif
chemokine ligand 1 (CXCL1), S100A8, S100A9, lipocalin 2, β-
defensin, and IL-6 in mice [19]. Taken together, these findings
indicate that psoriasis could be driven by a primary defect in
epidermal barrier function.
It has long been reported that psoriatic skin exhibits
malfunctioned epidermal barrier integrity along with disturbed
ceramides metabolism. Although it was once considered that
total ceramide level was not altered in psoriasis epidermis,
recent studies with improved measurement methods and larger
and more strictly controlled sample size have shown that
significantly decreased total ceramides are inversely correlated
with Psoriasis Area Severity Index (PASI) score [20]. VLC
ceramides are increased in psoriatic lesions, while ULC ceramides
are significantly decreased [21]. This bias towards shorter
ceramides contributes to hexagonal lipid organization and phase
separation in extracellular lipid membranes. Cer[NS] is elevated
in psoriatic lesions, whereas phytosphingosine-carrying ceram-
ides (phytoCer, such as Cer[NP] and Cer[AP]) and acylCer are both
reduced in psoriatic lesions and correlate with increased TEWL
and inferior water retention capacity [2]. PhytoCer enhances SC
barrier structure by forming strong hydrogen bonds and highly
thermostable domains in the extracellular lipid matrix [22].
4 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8

Thus, decreased phytoCer and acylCer, which are critical for
epidermal lipid lamellae structure and keratinocyte differentia-
tion, act as a causal role in permeability barrier dysfunction and
hyperproliferation in psoriasis. Furthermore, circulating levels of
total ceramides are decreased in psoriasis patients, while serum
S1P increased [23]. Presumably, decreased serum ceramides can
be ascribed to enhanced ceramide degradation, since S1P is a
derivative from ceramide hydrolysis. S1P promotes Th17 cell
development, IL-17 generation, trans-endothelial T cell migra-
tion, and angiogenesis [24]. Hence, ceramides and their
metabolites may exacerbate immune response in psoriatic
pathogenesis.
To investigate the mechanisms underlying the altered ceramide
expression profile in psoriasis, researchers have focused on the
enzymes in ceramide metabolism. SPT, the rate-limiting enzyme in
ceramide de novo synthesis, is decreased in psoriatic epidermis. A
study in SPT-cKO mice showed that a marked reduction of ceramides
in the epidermis leads to barrier dysfunction, upregulation of IL-17
and gd T cell expansion in the psoriasiform lesions [20]. β-
glucocerebrosidase (GlcCerase), CerS3, and elongase of long-chain
fatty acids (ELOVL) 1 are also downregulated in psoriatic lesions,
which can partially explain the decrease in acylCers and alteration of
permeability barrier function (Fig. 1) [25].
4.2. Atopic dermatitis
Epidermal barrier dysfunction has been observed in both
lesional and non-lesional skin sites of AD, manifested as enhanced
TEWL, raised skin pH, altered surface microbiota colonization
pattern, and disturbed ceramide profile. With regards to the total
level of SC ceramides, studies have reported a significant decrease
in lesional AD skin [26]. Yet, the composition rather than the
amount of ceramides is more strongly associated with disturbed
skin barrier function in AD. Studies have also found increased
relative levels of Cer[AS], Cer[AH], Cer[AP], Cer[ADS], and Cer[NS]
in AD lesions compared to healthy subjects, whereas decreased
levels of Cer[NP], Cer[NH], and acylCer [27]. Similar to the changes
of ceramide acyl chain length in psoriasis, AD skin also exhibits an
elevation in LC and VLC ceramides, particularly C18 ceramides, but
a reduction in ULC ceramides [28]. This altered composition of
epidermal ceramides correlate with downregulated levels of
natural moisturizing factor (NMF), enhanced TEWL, and increased
Severity Scoring of Atopic Dermatitis (SCORAD) index [5]. The
underlying attenuated barrier function in AD results in continuous
generation of cytokines and chemokines, a proinflammatory
cytokine cascade, and unimpeded intrusions of allergens and
antigens, which contributes to the "atopic march" [29]. Cer[EOS]/
Cer[NS] ratio is significantly lower in AD patients with food allergy
than those without food allergy [30]. These results indicate that
altered ceramide composition not only contributes to disrupted
barrier function but also inflammatory and allergic properties in
AD individuals.
Studies have reported raised SM deacylase and declined
sphingomyelinase in AD, which may cause a decrease in total
ceramides, Cer[NS], and Cer[AS] [27]. High levels of CerS4 in AD
contribute to the enhanced synthesis of the short-chain ceramides
[31]. P. aeruginosa and S. aureus, present in microflora of AD skin,
could produce ceramidase activated by sphingosine derived from
the host [32]. However, it is intriguing to explain the causal link
between the reduced ceramides and altered microflora, since a
depletion in ceramides was reported to enable S. aureus growth
[33]. Interestingly, it was uncovered that Th2 cytokines, interferon
(IFN) -g, and tumor necrosis factor (TNF) -α induce a decrease in
ULC ceramides and an increase in LC ceramides (<C20), indicating a

Fig. 1. Altered ceramide profile mediates the progress of psoriasis.

Reduced activity of ceramide synthesis enzymes, including GlcCerase, CerS3 and ELOVL1, leads to decreased acylCer and phytoCer, and increased Cer[NS] and short chain
ceramides(<C26) in psoriatic lesions. Disproportional ceramides are excreted into the extracellular space from lamellar bodies, contributing to disturbed lipid matrix
structure and epidermal barrier function. Besides, ceramides are actively involved in keratinocyte proliferation. Moreover, circulating S1P, ceramide metabolite, induces
angiogenesis, promotes Th17 cell development and cytokine generation, and exacerbates immune response in psoriatic skin.
 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8 5

vicious cycle between epidermal barrier dysfunction and cytokines
generation in AD pathogenesis (Fig. 2) [25,34].
4.3. Ichthyoses
Ichthyoses, a group set of hereditary diseases, display an
epidermal barrier abnormality, which parallels the severity of
the clinical phenotype. Most of causative genes are associated
with ceramide synthesis, especially acylCer, and CLE formation.
For example, patients who carry a mutation in PNPLA1 (patatin-
like phospholipase domain-containing protein 1), ELOVL1, or
CERS3, which are all directly involved in acylCer synthesis,
result in reduced ULC ceramides and impaired CLE structure
[35]. Mutations in ABHD5 (α/β hydrolase domain containing 5),
which enhances acylCer production, are involved in ichthyosis
symptoms of Chanarin-Dorfman syndrome. In Neu-Laxova
syndrome, patients also exhibit reduced SC ceramides due to
phosphoglycerate dehydrogenase deficiency [36]. Regardless of
the diverse etiology of these inherited disorders, almost all of
the ichthyoses ultimately end up with reduced total ceramide
and acylCer amount, and defects in the extracellular lipid
matrix, which drives epidermal hyperproliferation and kerati-
nization.
4.4. Netherton syndrome
Netherton syndrome, resulting from recessive mutations in
SPINK5 (serine protease inhibitor Kazal-type 5), is characterized
by the triad of congenital ichthyosis, hair shaft anomalies and
severe atopic diathesis. The total amount of SC ceramides in
patients with Netherton syndrome is reduced, with significantly
decreased Cer[NP] and acylCer. Cer[AS], Cer[NS] and Cer[AH]
show little difference compared to the healthy skin. C14-C20
ceramides are raised, particularly C34, which leads to reduced
LPP and augmented hexagonal packing. A study has revealed
that in Netherton syndrome, the expression of the β-glucocer-
ebrosidase and acid sphingomyelinase, enzymes involved in
ceramide salvage pathway, is much lower and more diffuse
throughout the epidermis [37]. This altered enzyme activity
may be resulted from increased pH in the SC or unregulated
kallikrein activity.
4.5. Acne
Average ceramide chain length is significantly decreased in acne
lesions, contributing to dryness and irritation in acne patients.
Applying external ceramides within moisturizers among 29 acne
patients presents significantly reduced lesions, increased amount
and chain length of SC ceramides, and alleviated skin barrier with
reduced TEWL [38]. Besides, circulating levels of ceramide chain
length are reduced, while C16 SM and ceramide-1-phosphate levels
are elevated in acne patients compared to healthy controls,
indicating a systemic disturbed ceramide metabolism [39]. Studies
have revealed the properties of ceramide composition governing S.
aureus growth on SC, yet little has been known about effects of
ceramide profile on P. acnes and its pathogenic roles in acne [33].
4.6. Skin aging
Skin aging is characterized by flattening of the dermal-
epidermal junction, decreasing and disorganization of the
extracellular matrix. SC ceramide content and Cer[EOS] decline
significantly with age [2]. Interestingly, the rate of altered
ceramides is almost the same for both sun-exposed skin and

Fig. 2. Alteratered ceramide profile is actively involved in the pathogenesis of AD.

Increased ceramidase, SM deacylase, and CerS4 account for the reduction of total ceramide amount and increased short chain ceramides (<24C) in lamellar bodies. Besides,
Cer[AS] and Cer[NS] are elevated, whereas Cer[NP], Cer[NH], and acylCer are reduced. The altered ceramide profile leads to a less dense extracellular lipid matrix and
increased risks for external intrusions, which stimulates Th2/Th22 inflammation. Besides, disturbed ceramide profile and impaired barrier function itself can lead to
continuous generation of cytokines and chemokines, such as IL-1α, TNF-α, and β-defensin, exacerbating inflammation in AD.
6 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8

sun-protected skin, which indicates an intrinsic alteration of
ceramide metabolism in skin aging [40]. Topical supplementation
of ceramides inhibited wrinkle formation and reduced TEWL in
aged skin, suggesting a critical role of ceramides in delaying skin
aging [41]. Further studies need to clarify the mechanism by which
ceramides exert anti-aging effects.
4.7. Pruritus
Pruritus is associated with many chronic skin disorders and
are commonly seen in elderly individuals. The sensation of itch
can arise from the activation of epidermal nerve fibers, which
requires exogenous penetrating pruritogens or endogenous
mediators activating protease-activated receptor and transient
receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1,
respectively). Ceramides can maintain epidermal barrier integri-
ty, reduce penetration of pruritogens, provide itch relief and
improve quality of life [42]. Sphingomyelinase, an enzyme that
produce ceramides, was shown to inhibit TRPV1 and TRPA1
induced Ca2+ and calcitonin gene related peptide release, while
ceramides exhibited little influence on TRPA1 and TRPV1
activation in trigeminal neurons and TRPV1-expressing CHO cell
line [43]. Nevertheless, functions of ceramides toward TRPV1 and
TRPA1 may show a different picture in itch-associated unmyelin-
ated C fibers and requires investigation in future studies.
Altogether, these studies provide evidence for the multifunctional
role of ceramides in the pathogenesis of various inflammatory
dermatoses (Table 1).
5. Ceramides in the treatment of psoriasis and AD
Recent studies have discovered decreased SC ceramide content
and SC hydration as contributors of inflammation in aging, obesity,
and other systemic disorders. Man et al. have pointed out that
aberrant epidermal permeability barrier provokes an elevation in
both cutaneous and circulating cytokine levels, independent of
hepatic or T cell involvement [44]. Improving epidermal barrier
function alone, by topical application of an emollient, could reduce
circulating levels of proinflammatory cytokines, such as IL-1β, IL-6,
and TNF-α [45]. Hence, maintaining epidermal homeostasis may
possess therapeutic promises for dermatoses with systemic
inflammation, such as psoriasis and AD.
Previous studies have shown that topical application of phytoCer
or its analogues (phytosphingosine maleic and fumaric acid amides)
increases NMF and skin hydration, decreases skin inflammation in
keratinocytes, and ameliorates IL-23-induced psoriasiform derma-
titis in mouse ears [3]. A recent study among 106 psoriasis vulgaris
patients implicated that topical application of linoleic acid-ceramide
moisturizer is effective for both treatment and prevention of
psoriasis [46]. Worthy to note that ceramides must be delivered
with cholesterol and fatty acids in an appropriate ratio and sufficient
amount to impart barrier improvements, otherwise barrier function
would be deteriorated [29].
Therapeutic effects of ceramides are also frequently studied
in AD. Ceramides were shown to prevent the downregulation of
filaggrin and disorganization of keratin 10 and β4-integrin in an
AD-like 3D human skin model [47]. Topical application of
linoleic acid-ceramide moisturizer also show promising effects
in AD patients, by significantly improving skin capacitance,
TEWL, Eczema Assessment Severity Index (EASI) and pruritus
scores [48]. Moreover, ceramide-containing moisturizers can
minimize corticosteroid exposure, prevent corticosteroid side-
effects and reduce AD flares, via stimulating peroxisome
proliferator-activated receptor (PPAR) α expression, reducing
inflammation, and enhancing antimicrobial peptides expression
[49]. A randomized trial in infants with high risk of AD proved that
topical application of ceramide dominant emollient prevents
development of AD and food sensitization [50]. Thus, application
of ceramides offers more than a therapeutic relief of symptoms,
but also preventive measures in the development of psoriasis
and AD.
6. Conclusion
Ceramides, the main element of extracellular lipid in SC, exert
various roles in skin homeostasis, including epidermal barrier
maintenance, epidermal self-renewal, and immune modulation.
Ceramide expression varies among classes in both normal and
diseased skin. Impaired ceramide expression profile is associated
with increased TEWL, inferior water capacity of SC, and enhanced
inflammation. Evidence from both in vivo and in vitro studies have
uncovered promising effects of ceramides in enhancing perme-
ability barrier and alleviating skin inflammatory and immune
responses. The challenge for future studies is to understand the
precise mechanism of epidermal ceramides in inflammatory
cytokines cascade and immune cells infiltration to the skin, which
further facilitates new therapeutic strategies in inflammatory skin
diseases.

Table 1
Expression profile and function of epidermal ceramides in inflammatory dermatoses.

Inflammatory Ceramide expression profile Roles and functions References

dermatoses
Psoriasis Cer[NS], [AS], short chain ceramides" enhance barrier function, restrict keratinocyte proliferation, prevent Tawada et al. 2014 [21];
[NP], [AP], acylCer, long chain ceramides# barrier-induced inflammation response Mysliwiec et al. 2017 [23]
AD Cer[AS], Cer[AH], Cer[AP], Cer[ADS], and reduce TEWL, prevent barrier-induced proinflammatory cytokine cascade, van Smeden et al. 2014 [28];
Cer[NS], short chain ceramides" protect against intrusions of allergens and antigens Elias et al. 2019 [30]
Cer[NP], Cer[NH], and acylCer, long chain
ceramides#
Ichthyoses CER [EOS], [NP], CER[AP], and CER[AH] # maintain epidermal CLE structure, reduce TEWL, restrain keratinocyte Mueller et al. 2019 [35]
proliferation
Netherton short chain ceramides, unsaturated maintain extracellular lipid packing structure, reduce TEWL van Smeden et al. 2014 [37]
syndrome ceramides, glucosylceramides"
Cer[NP] and acylCer#
Acne ceramide chain length# maintain epidermal barrier function, increase SC hydration influencing Isoda et al. 2015 [38]
growth of P. acnes?
Skin aging total ceramides and Cer[EOS]# inhibit wrinkle formation, hold SC hydration capacity Lueangarun et al. 2019 [41]
Pruritus Unknown maintain barrier integrity, reduce pruritogens penetration preventing Zirwas et al. 2017 [42]
TRPV1 or TRPA1 activation?
 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8
Funding
This work was supported by the National Natural Science
Foundation of China (nos. 81673051 and 81872519).
Declaration of Competing Interest
The authors have no conflict of interest to declare.
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8 Q. Li et al. / Journal of Dermatological Science 97 (2020) 2–8

[48] Q. Yang, M. Liu, X. Li, et al., The benefit of a ceramide-linoleic acid-containing

moisturizer as an adjunctive therapy for a set of xerotic dermatoses, Dermatol. Qingyang Li is an M.D. student at Fourth Military Medical
Ther. 32 (2019)e13017. University, China. She works in the team of Prof. Gang
[49] S.E. Lee, M.K. Jung, S.J. Oh, et al., Pseudoceramide stimulates peroxisome Wang in the Department of Dermatology, Xijing Hospital,
proliferator-activated receptor-alpha expression in a murine model of atopic Fourth Military Medical University. She specializes in cell
dermatitis: molecular basis underlying the anti-inflammatory effect and the biology, mitochondria function, and lipid metabolism.
preventive effect against steroid-induced barrier impairment, Arch. Dermatol. Her research interest focuses on epidermal barrier,
Res. 307 (2015) 781–792. ceramides, and vascular endothelial cells in the patho-
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replacement strategy for the prevention of atopic dermatitis and allergic
sensitization: the PEBBLES pilot study, Br. J. Dermatol. 178 (2018) e19–
e21.