Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of nonscarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

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Apremilast Use for Moderate-to-Severe Atopic Dermatitis in Pediatric Patients

Case Reports in Dermatology ◽

10.1159/000446836 ◽

2016 ◽

Vol 8 (2) ◽

pp. 179-184 ◽

Cited By ~ 19

Author(s):

Rachael C. Saporito ◽

David J. Cohen

Keyword(s):

Atopic Dermatitis ◽

Case Report ◽

Immunoglobulin E ◽

Interleukin 4 ◽

Severe Atopic Dermatitis ◽

T Helper ◽

Novel Therapy ◽

T Helper 2 ◽

American Children ◽

Bacterial Superinfection

Atopic dermatitis (AD) is a chronic, pruritic skin disease often complicated by bacterial superinfection affecting 10.7% of American children. The pathogenesis involves a skin barrier breakdown in addition to dysfunctional innate and adaptive immune response, including an unbalanced increase in T-helper 2 cells and hyperimmunoglobulinemia E. The increased numbers of T-helper 2 cells are involved in stimulating the production of immunoglobulin E and eosinophilia by releasing interleukin-4, -5, and -13 as well as in decreasing protection against bacterial superinfection by releasing interleukin-10. The current Food and Drug Administration-approved symptomatic treatment for AD includes topical ointments, topical and systemic corticosteroids, topical immunomodulant therapy, antibiotics, and phototherapy, but there are not approved targeted therapies or cures. By presenting a case of an 8-year-old African-American boy, this case report supports novel therapy of moderate-to-severe AD with apremilast, a phosphodiesterase type 4 inhibitor. Apremilast has recently completed the phase 2 clinical trial (NCT02087943) for treatment of AD in adults. This case report illustrates the potential for apremilast as a treatment for AD in children, where there is a great need for safe and effective medications.

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OX40L–OX40 Signaling in Atopic Dermatitis

Journal of Clinical Medicine ◽

10.3390/jcm10122578 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2578

Author(s):

Masutaka Furue ◽

Mihoko Furue

Keyword(s):

T Cells ◽

Atopic Dermatitis ◽

Memory T Cells ◽

Effector Memory ◽

T Helper ◽

T Helper 1 ◽

Therapeutic Success ◽

T Helper 2 ◽

Promising Target ◽

Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

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Targeting the T Helper 2 Inflammatory Axis in Atopic Dermatitis

International Archives of Allergy and Immunology ◽

10.1159/000451083 ◽

2016 ◽

Vol 171 (2) ◽

pp. 71-80 ◽

Cited By ~ 17

Author(s):

Adriana S. Moreno ◽

Roderick McPhee ◽

Luisa Karla Arruda ◽

Michael D. Howell

Keyword(s):

Atopic Dermatitis ◽

T Helper ◽

T Helper 2

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Association of a New-Type Prostaglandin D2 Receptor CRTH2 with Circulating T Helper 2 Cells in Patients with Atopic Dermatitis

Journal of Investigative Dermatology ◽

10.1046/j.1523-1747.2002.01862.x ◽

2002 ◽

Vol 119 (3) ◽

pp. 609-616 ◽

Cited By ~ 65

Author(s):

Masahiro Iwasaki ◽

Kinya Nagata ◽

Shoichi Takano ◽

Kazuo Takahashi ◽

Norihisa Ishii ◽

...

Keyword(s):

Atopic Dermatitis ◽

D2 Receptor ◽

Prostaglandin D2 ◽

T Helper ◽

T Helper 2 ◽

New Type

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A novel mouse model of atopic dermatitis that is T helper 2 (Th2)-polarized by an epicutaneous allergen

Environmental Toxicology and Pharmacology ◽

10.1016/j.etap.2017.12.025 ◽

2018 ◽

Vol 58 ◽

pp. 122-130 ◽

Cited By ~ 4

Author(s):

Hyun Jung Park ◽

Wahn Soo Choi ◽

Won Young Lee ◽

Youngsok Choi ◽

Chankyu Park ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mouse Model ◽

T Helper ◽

T Helper 2

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Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Atopic Dermatitis Symptoms in Mice

Mediators of Inflammation ◽

10.1155/2018/9079527 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Jae Gwang Park ◽

Young-Su Yi ◽

Sang Yun Han ◽

Yo Han Hong ◽

Sulgi Yoo ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mrna Expression ◽

Pharmacological Activity ◽

Proinflammatory Cytokines ◽

Proinflammatory Cytokine ◽

Immunoglobulin E ◽

Ethanol Extract ◽

Underlying Mechanism ◽

T Helper ◽

T Helper 2

Tabebuia avellanedae has been traditionally used as an herbal remedy to alleviate various diseases. However, the plant’s pharmacological activity in allergic and inflammatory diseases and its underlying mechanism are not fully understood. Therefore, we investigated the pharmacological activity of Tabetri (T. avellanedae ethanol extract (Ta-EE)) in the pathogenesis of AD. Its underlying mechanism was explored using an AD mouse model and splenocytes isolated from this model. Ta-EE ameliorated the AD symptoms without any toxicity and protected the skin of 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice from damage and epidermal thickness. Ta-EE reduced the secreted levels of allergic and proinflammatory cytokines, including histamine, immunoglobulin E (IgE), interleukin- (IL-) 4, and interferon-gamma (IFN-γ) in the DNCB-induced AD mice. Ta-EE suppressed the mRNA expression of T helper 2-specific cytokines, IL-4 and IL-5, and the proinflammatory cytokine IFN-γ in the atopic dermatitis skin lesions of AD mice. Moreover, Ta-EE suppressed the mRNA expression of IL-4, IL-5, IFN-γ, and another proinflammatory cytokine, IL-12, in the Con A-stimulated splenocytes. It also suppressed IL-12 and IFN-γ in the LPS-stimulated splenocytes. Taken together, these results suggest that Ta-EE protects against the development of AD through the inhibition of mRNA expression of T helper 2-specific cytokines and other proinflammatory cytokines.

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