IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases

Abstract

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet’s disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine—it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders.

IL-33/IL-31 Axis in Osteoporosis

“…IL-31 exerts central roles in the pathogenesis and progression of atopic dermatitis and chronic spontaneous urticaria. IL-31, released by CD45RO+ Th2 lymphocytes but also by macrophages, dendritic and eosinophilic cells, mediates the itching in patients suffering from allergic diseases, whereas IL-33, secreted by inflamed or damaged tissue, functions as a local early warning signal [43]. However, although IL-31 primarily induces Th2 responses and allergic manifestations [44], it also suppresses Th2 inflammation [45].…”

“…IL-33 activates naive T cells and promotes their maturation towards a Th2 phenotype, leading to the release of Th2 type cytokines and chemokines. IL-33 influences various adaptive and innate immune cells, including eosinophils, mast cells, type 2 innate lymphoid cells (ILC2), and Th2 lymphocytes [42][43][44]. Via the NF-kB and MAPK signaling pathways, IL-33 induces the production of IL-5, IL-13 and CCL5, CCL17, CCL24 chemokines [57,65].…”

“…Figure 2 illustrates the role of IL-33 in bone remodeling. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of anti-osteoclastic genes, such as interferon regulatory factor-8 (IRF-8), which can be blocked by an anti-ST2 monoclonal antibody [43]. IL-33 acts on all different types of bone cells [64].…”

Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy

“…Recently was suggested that the IL-31/IL-33 axis could be involved in different conditions such as cancer, autoimmune diseases and allergies [31]. So, this is another interesting and new area to investigate among the complex overlapping mechanisms that connect allergies and osteoporosis (Table 1).…”

“…So, this is another interesting and new area to investigate among the complex overlapping mechanisms that connect allergies and osteoporosis (Table 1). Interleukin-31 (IL-31) is a proinflammatory cytokine, recently indicated as a biomarker of allergic and immunologic diseases, that regulates cell proliferation and play a role in tissue remodelling [31]. It is produced by CD4+ T lymphocytes (Th2 cells) and in lower amounts also by dendritic cells and mast cells.…”