Interleukin-31 receptor (IL-31R) (IL-31R)

The Interleukin-31 receptor (IL-31R) is a heterodimeric signaling complex consisting of the Interleukin-31 receptor subunit alpha (IL-31RA) and the Oncostatin M receptor (OSMR) beta subunit (Dillon et al., 2004, PMID: 15184896). It is predominantly expressed on various cell types including keratinocytes, cutaneous sensory neurons, and activated immune cells like macrophages and T cells (Cevikbas et al., 2014, PMID: 24373353). The primary biological function of IL-31R is to mediate the effects of the cytokine IL-31, which involves the activation of the JAK/STAT, MAPK, and PI3K/AKT signaling pathways (Zhang et al., 2008, PMID: 18432274). This receptor complex is a key driver of pruritus (itch) and skin inflammation, playing a central role in the pathophysiology of chronic conditions such as atopic dermatitis and prurigo nodularis (Sonkoly et al., 2006, PMID: 16461139). By transmitting signals to dorsal root ganglia, IL-31R directly links the immune system to the nervous system to induce the itch sensation (Cevikbas et al., 2014, PMID: 24373353). Therapeutic intervention typically involves monoclonal antibodies, such as nemolizumab, which targets the IL-31RA subunit to block IL-31 binding and interrupt the itch-scratch cycle (Ruzicka et al., 2017, PMID: 28249150). Clinical studies have demonstrated that inhibiting this receptor significantly reduces itch intensity and improves skin barrier function in patients with inflammatory skin diseases (Yosipovitch et al., 2020, PMID: 32032494).

Other names

IL-31RA/OSMR complexInterleukin-31 receptor subunit alpha (IL31RA)Oncostatin M receptor (OSMR)GP130-like receptor (GPL)Cytokine receptor-like 3 (CRL3)Glioma-associated monocyte antigen (GLM-R)

Antagonism of the receptor complex via monoclonal antibodies that bind to specific subunits (e.g., IL-31RA or OSMR), thereby blocking the binding of the IL-31 ligand and inhibiting downstream pro-inflammatory and pruritogenic signaling cascades.