Development of a novel antibody therapy for improving itch and inflammation in atopic dermatitis: Wakayama Medical University confirmed the effect in mice

A research group led by Professor Yoshihiro Morikawa of the Department of Anatomy and Neurobiology at Wakayama Medical University investigated the role of oncostatin M (OSM) in the pathology of atopic dermatitis, using a mouse model of the skin condition. They demonstrated that a monoclonal antibody (mAb) against OSM receptor beta subunit (OSMRβ), a common receptor subunit for OSM and interleukin (IL)-31, has a significant therapeutic effect. The study results were published in The FASEB Journal, the official journal of the Federation of American Societies for Experimental Biology, on December 16, 2023.

IL-31 is one of the critical cytokines involved in the development of pruritus and skin lesions in atopic dermatitis. However, inhibition of the IL-31 signal does not improve the skin lesions seen in the disease. ILs, of which 41 types (IL-1−41) have been reported, are a group of cytokines that are mainly involved in interactions between leukocytes. Among them, IL-4, IL-13, and IL-31 are particularly involved in the development and exacerbation of atopic dermatitis. As one of the cytokines in the IL-6, OSM is involved in the pathology of various types of inflammatory diseases and cancers.

The research group found that in a mouse model of atopic dermatitis, the administration of OSM exacerbated the skin lesions and increased IL-4 production in the lymph nodes, whereas treatment with an anti-OSMRβ mAb (7D2) alleviated skin inflammation of the back, auricle (outer ear), and face. In addition to alleviating their skin lesions, the 7D2 mAb reduced the scratching behavior of the mice and decreased the number of OSMRβ-positive neurons in the dorsal root ganglia. Moreover, the 7D2 mAb reduced the serum concentrations of IL-4, IL-13, and immunoglobulin E (IgE, a type of antibody that binds to allergens and causes type I allergy) and the lymph node expression of the IL-4 and IL-13 genes in the mice. Blocking both IL-31 and OSM signaling suppressed the pruritis and T helper type 2 (a subset of immune T cells) responses, leading to alleviation of the skin lesions of atopic dermatitis. The anti-OSMRβ mAb may be a novel therapeutic candidate for treating atopic dermatitis.

Morikawa explained, "Atopic dermatitis not only causes significant impairment of quality of life, including sleep disturbance due to intense itching, but is also detrimental to social life owing to the eczema that often manifests on the face and neck. The effectiveness of common treatments for pruritus and skin inflammation is low, especially for moderate to severe atopic dermatitis. Although antibody drugs such as Dupilumab and Nemolizumab have been developed, their high cost is a drawback to their wide application. While the continued development of antibody drugs that are effective in the short term and in low doses is desired, we expect the antibody found in this study to be a strong candidate."

Journal Information
Publication: The FASEB Journal
Title: Blockade of OSMRβ signaling ameliorates skin lesions in a mouse model of human atopic dermatitis
DOI: 10.1096/fj.202301529R