Skin Barrier Dysfunction and Low Antimicrobial Peptide Expression in Cutaneous T-cell Lymphoma

Suga, Hiraku; Sugaya, Makoto; Miyagaki, Tomomitsu; Ohmatsu, Hanako; Kawaguchi, Makiko; Takahashi, Naomi; Fujita, Hideki; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Sato, Shinichi

doi:10.1158/1078-0432.ccr-14-0077

Cited by 49 publications

(55 citation statements)

References 52 publications

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“…We found some discrepancies between our finding and those of and other studies [11] that might be related to our relatively small study group with only a few cases of advanced-stage CTCL, which is a limitation of our study. Moreover, the major limitation is the disparity in the number of samples from female and male volunteers between the control, CTCL and AD groups.…”

Section: Limitations Of This Studycontrasting

confidence: 97%

“…However, reports concerning their role in CTCL are rather scarce. There is only one study, by Suga et al, that has analyzed skin barrier dysfunction in CTCL [11]. Decreased levels of FLG and LOR mRNA have already been demonstrated in the skin of CTCL and psoriasis patients, which confirms that skin barrier dysfunction is not specific to AD pathogenesis [11].…”

Section: Discussionmentioning

confidence: 99%

“…Both MF and AD show infiltration of the skin by skin-homing T-cells [10,11]. The skin of MF patients similar to AD shows an impaired skin barrier with decreased expression of filaggrin, loricrin and antimicrobial peptides in the skin, which results in increased susceptibility towards Staphylococcus aureus colonization and infections [11,12]. The malignant T-cells were reported to be responsible for changes in the epidermis in CTCL and impaired epidermal barrier function [13].…”

Section: Introductionmentioning

confidence: 99%

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Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

et al. 2020

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The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of FLG, FLG2, RPTN, HRNR, SPRR1A, SPRR1B, SPRR3 and LELP-1 mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples. We have found that mRNA levels of FLG, FLG2, LOR, CRNN and SPRR3v1 were decreased (p ≤ 0.04), whereas mRNA levels of RPTN, HRNR and SPRR1Av1 were increased in lesional and nonlesional AD skin compared to the healthy control group (p ≤ 0.04). The levels of FLG, FLG2, CRNN, SPRR3v1 mRNA increased (p ≤ 0.02) and RPTN, HRNR and SPRR1Av1 mRNA decreased (p ≤ 0.005) in CTCL skin compared to the lesional AD skin. There was a strong correlation between the stage of CTCL and increased SPRR1Av1 gene expression at both mRNA (R = 0.89; p ≤ 0.05) and protein levels (R = 0.94; p ≤ 0.05). FLG, FLG2, RPTN, HRNR and SPRR1A seem to play a key role in skin barrier dysfunction in CTCL and could be considered a biomarker for differential diagnosis of AD and CTCL. SPRR1Av1 transcript levels seem to be a possible marker of CTCL stage, however, further studies on a larger study group are needed to confirm our findings.

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Section: Limitations Of This Studycontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

et al. 2020

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“…10,17,27 IL-25 expression on those epithelial cells is known to be induced by environmental allergens derived from Aspergillus oryzae and ragweed. 10,26 As skin barrier dysfunction is shown in CTCL, 28 as well as AD, such allergens can cause upregulation of IL-25 expression by epidermal keratinocytes. Other than environmental factors, IL-25 mRNA expression was upregulated in HaCaT cells, one of the cell lines of epidermal keratinocytes, after IL-4 stimulation, 19 suggesting that Th2 cytokines can regulate IL-25 expression on epidermal keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment

et al. 2018

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“…In atopic dermatitis, reduced production of antimicrobial peptides in the skin accounts for frequent infections and impaired cutaneous immune response. Of interest are two studies by Suga et al and Wolk et al [30,31] that show lower expression levels of antimicrobial peptides in lesional CTCL skin. Beside tumor-derived galectins, low level of antimicrobial peptides in CTCL, as in atopic dermatitis, correlated with barrier dysfunction and frequent infections of the skin.…”

Section: Recent Immunological Studiesmentioning

confidence: 99%

Recent advances in primary cutaneous T-cell lymphoma

DeSimone

Sodha

Ignatova

et al. 2015

Current Opinion in Oncology

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PURPOSE OF REVIEW Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. RECENT FINDINGS In the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SUMMARY This is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year. Purpose of review Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. Recent findingsIn the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SummaryThis is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year.

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Skin Barrier Dysfunction and Low Antimicrobial Peptide Expression in Cutaneous T-cell Lymphoma

Cited by 49 publications

References 52 publications

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment

Recent advances in primary cutaneous T-cell lymphoma

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