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

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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Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis

Skin Appendage Disorders ◽

10.1159/000517832 ◽

2021 ◽

pp. 1-4

Author(s):

Maurizio Romagnuolo ◽

Mauro Barbareschi ◽

Simona Tavecchio ◽

Luisa Angileri ◽

Silvia Mariel Ferrucci

Keyword(s):

Atopic Dermatitis ◽

Skin Disorder ◽

Human Monoclonal Antibody ◽

Severe Atopic Dermatitis ◽

T Helper ◽

T Helper 1 ◽

Th2 Response ◽

Alopecia Universalis ◽

T Helper 2 ◽

Relapsing Remitting

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

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2016.07.047 ◽

2017 ◽

Vol 76 (1) ◽

pp. 91-97.e3 ◽

Cited By ~ 19

Author(s):

Doris Weiss ◽

Michaela Schaschinger ◽

Robin Ristl ◽

Robert Gruber ◽

Tamara Kopp ◽

...

Keyword(s):

Atopic Dermatitis ◽

Severe Atopic Dermatitis ◽

T Helper ◽

Down Regulation ◽

T Helper 2

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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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Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells

Journal of Experimental Medicine ◽

10.1084/jem.20061196 ◽

2007 ◽

Vol 204 (2) ◽

pp. 357-367 ◽

Cited By ~ 145

Author(s):

Hamida Hammad ◽

Mirjam Kool ◽

Thomas Soullié ◽

Shuh Narumiya ◽

François Trottein ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Airway Inflammation ◽

Cell Function ◽

Interleukin 10 ◽

Prostaglandin D2 ◽

T Helper ◽

T Helper 2 ◽

Novel Treatments ◽

Dependent Protein

Prostaglandins (PGs) can enhance or suppress inflammation by acting on different receptors expressed by hematopoietic and nonhematopoietic cells. Prostaglandin D2 binds to the D prostanoid (DP)1 and DP2 receptor and is seen as a critical mediator of asthma causing vasodilation, bronchoconstriction, and inflammatory cell influx. Here we show that inhalation of a selective DP1 agonist suppresses the cardinal features of asthma by targeting the function of lung dendritic cells (DCs). In mice treated with DP1 agonist or receiving DP1 agonist-treated DCs, there was an increase in Foxp3+ CD4+ regulatory T cells that suppressed inflammation in an interleukin 10–dependent way. These effects of DP1 agonist on DCs were mediated by cyclic AMP–dependent protein kinase A. We furthermore show that activation of DP1 by an endogenous ligand inhibits airway inflammation as chimeric mice with selective hematopoietic loss of DP1 had strongly enhanced airway inflammation and antigen-pulsed DCs lacking DP1 were better at inducing airway T helper 2 responses in the lung. Triggering DP1 on DCs is an important mechanism to induce regulatory T cells and to control the extent of airway inflammation. This pathway could be exploited to design novel treatments for asthma.

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