The skin is a dynamic organ that involves a variety of cells that renders protective barrier, immunity and sensation toward environmental insults. However, in chronic inflammation, numerous homeostatic processes get dysregulated. Current advances in skin immunology have disclosed new innate immune and neuroimmune mechanisms that are energetically altering conventional paradigms of the pathophysiology underlying different inflammatory skin disorders. 

Exploring innate immunity has given insights into the pathophysiology of atopic dermatitis, allergic contact dermatitis and chronic spontaneous urticaria.

Seminal findings of the mechanisms underlying neuroimmune crosstalk have recognized novel targets for medical intervention and have also provided a rationale for the insufficient efficacy of previous treatment modalities. Newly recognized pathways like the Mas-related G protein-coupled receptor B2 (MRGPRB2) and Mas-related G protein-coupled receptor X2 (MRGPRX2)-mast cell signaling axis, have explained the flaws of IgE and histamine blockade in treating pruritic disorders like allergic contact dermatitis, chronic spontaneous urticaria and contact urticaria, while simultaneously highlighting the potential contribution of MRGPRB2/X2 biology in chronic spontaneous urticaria and contact urticaria. These pathways have shown the involvement of mast cells in an assortment of pruritic skin disorders.

Type 2 cytokine blockade and Janus kinase (JAK) inhibition are the prime advancements in the treatment of inflammatory skin disorders like atopic dermatitis.

Similar to JAK inhibitors′ potential to redefine the management of chronic inflammatory skin orders, MRGPRB2/X2 immunomodulatory agents may also make a cutting edge of dermatology and clinical allergy and immunology in the coming years.

Source: Abreu D, Kim BS. Innate immune regulation of dermatitis. Immunol Allergy Clin North Am. 2021;41(3):347-59.