Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis

Abstract

Purpose Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. Methods ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. Results We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4 + effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. Conclusions These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.

Efficacy of Dupilumab in Concomitant Atopic Dermatitis and Chronic Rhinosinusitis With Nasal Polyps: A Preliminary Study

“…The IgG4 monoclonal antibody dupilumab targets the interleukin-4 receptor alpha chain (IL-4Rα), thus inhibiting the biological effects of the cytokines IL-4 and IL-13 essential for the Th2 response. 1 2 3 We performed a prospective observational real-life study to evaluate the efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) associated with moderate-to-severe atopic dermatitis (msAD).…”

Capsaicin: Plants of the Genus <b><i>Capsicum</i></b> and Positive Effect of Oriental Spice on Skin Health

“…AD is a multiplex disease that has a genetic predisposition combined with an immune response as well as environmental factors [71]. Previous studies documented that various animal models have been developed for the investigation of AD [72]. A study was conducted by Back et al [68] on a rat model; in this model, symptom development after weaning is followed by increases in the levels of serum IgE and skin NGF, IL-4, and IL-13 at approximately 3 weeks after injection [73].…”

Comparative Study on Different Skin Pruritus Mouse Models

“…An imiquimod-induced psoriasis model is used to imitate the symptoms of patients with psoriasis in the clinic ( 17 , 18 ). It has been reported that disturbances in the innate and adaptive cutaneous immune responses are responsible for the development and sustainment of psoriatic inflammation ( 19 , 20 ).…”

“…Multiple pharmaceuticals could reduce cytokines and chemokines including histamine, TSLP, IL-5, IL-6, IL-8, and IL-13 to relieve the pruritus of the AD induced by DNFB ( 35 , 36 ). The levels of serum IgE, IL-4, and AD-involved cytokines, such as TNFα, interferon-γ (IFN-γ), IL-1β, TSLP, IL-33, and IL-25, also mediate inflammation in an oxazolone-induced mouse model ( 19 , 37 ). Different cytokines and chemokines, such as interleukin, TNFα, INFγ, and monocyte chemotactic protein 1 (MCP-1), also increased in imiquimod-induced psoriasis ( 38 , 39 ).…”

“…The levels of serum IgE, IL-4, and AD-involved cytokines, such as TNFα, interferon-γ (IFN-γ), IL-1β, TSLP, IL-33, and IL-25, also mediate inflammation in an oxazolone-induced mouse model (19,37). Different cytokines and chemokines, such as interleukin, TNFα, INFγ, and monocyte chemotactic protein 1 (MCP-1), also increased in imiquimod-induced psoriasis (38,39).…”