Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model.
Topical steroids and antihistamines are commonly used for the treatment of atopic dermatitis (AD). However, in a substantial number of patients with AD, these treatments are not sufficiently effective. In AD patients, C-fibers in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. To investigate the effect of Sema3A on AD, we administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in: (a) epidermal thickness; (b) the density of invasive nerve fibers in the epidermis; (c) inflammatory infiltrates, including mast cells and CD4+ T cells; and (d) the production of IL-4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch cycle likely contributes to the improvement of the AD-like skin lesions, Sema3A is promising in the treatment of patients with refractory AD, as well as overall itching dermatosis.
Yamaguchi
Junko
J
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Nakamura
Fumio
F
Aihara
Michiko
M
Yamashita
Naoya
N
Usui
Hiroshi
H
Hida
Tomonobu
T
Takei
Kohtaro
K
Nagashima
Yoji
Y
Ikezawa
Zenro
Z
Goshima
Yoshio
Y
D000818:Animals; D001369:Axons / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D040121:Semaphorin-3A / Q000378:metabolism / Q000502:physiology*
D011994:Recombinant Proteins; D040121:Semaphorin-3A; D039942:Neuropilin-1; D015847:Interleukin-4