MicroRNA‐155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells

Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing inflammatory dermatosis characterized by pruritus, xerosis, and a close association with IgE mediated sensitization to aeroallergens and foods. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). The distribution of lesions varies by age. Infants tend to have lesions on the cheeks and scalp, and very young children typically have involvement over the extremities, cheeks, forehead, and neck. A rash in the diaper area of infants is rarely AD. Lesions in older children and adults are usually located in flexural areas, such as the antecubital and popliteal fossae, along with the head and neck. Acute lesions of AD begin as erythematous papules and serous exudates. Secondary lesions include excoriations and crusted erosions due to scratching. Subacute lesions appear as erythematous scaling papules and plaques. If the itch and rash progress uncontrolled, then chronic lichenified AD develops, which features accentuated skin markings with hyperpigmentation. Trigger avoidance, skin hydration, and topical steroids are the first steps for improvement. In acute lesions of AD, the T-helper type 2 cells produce interleukin (IL) 4, IL-13, and IL-31, which may potentiate barrier dysfunction and contribute to pruritus. In chronic lesions, the T-helper type 1 cells predominate and secrete interferon γ and IL-12. Barrier dysfunction from filaggrin predisposes patients to AD. Skin superinfection, particularly with Staphylococcus aureus, is common, and cultures of affected lesions help guide therapy. Eczema herpeticum from herpes simplex virus can be life threatening in patients with AD.

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T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Endocrinology ◽

10.1210/en.2009-0434 ◽

2009 ◽

Vol 150 (11) ◽

pp. 5135-5142 ◽

Cited By ~ 51

Author(s):

Ichiro Horie ◽

Norio Abiru ◽

Yuji Nagayama ◽

Genpei Kuriya ◽

Ohki Saitoh ◽

...

Keyword(s):

Immune Response ◽

Autoimmune Thyroiditis ◽

Th17 Cells ◽

Intermediate Phenotype ◽

Lymphocyte Infiltration ◽

Wild Type ◽

T Helper ◽

Nonobese Diabetic ◽

Th2 Immune Response ◽

Helper Type

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.

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Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.811600 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shigeki Katoh

Keyword(s):

Monoclonal Antibodies ◽

Airway Inflammation ◽

Th17 Cells ◽

Acute Asthma ◽

Mite Allergen ◽

Th2 Cells ◽

T Helper ◽

Th2 Cell ◽

Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

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