Interleukin-31 receptor subunit alpha:Oncostatin-M receptor subunit beta complex (IL-31RA:OSMRβ complex)

The Interleukin-31 receptor subunit alpha:Oncostatin-M receptor subunit beta complex (IL-31RA:OSMRβ) is a heterodimeric type I cytokine receptor that mediates the signaling of Interleukin-31 (IL-31) [1, 2]. It is composed of the IL-31RA subunit, which binds IL-31 with high affinity, and the OSMRβ subunit, which is shared with the Oncostatin M receptor and is essential for signal transduction [1, 32]. Activation of this complex primarily triggers the JAK/STAT pathway (specifically JAK1/2 and STAT3/5), along with the PI3K/AKT and MAPK signaling cascades [5, 39]. These pathways are critical for regulating Th2-mediated immune responses and facilitating neuroimmune communication between the immune system and sensory nerves [10, 33]. The complex is highly expressed on keratinocytes and dorsal root ganglia neurons, where it acts as a key mediator of chronic pruritus (itch) [6, 13]. Pathologically, it is a central driver of symptoms in inflammatory skin conditions such as atopic dermatitis and prurigo nodularis [6, 38]. Therapeutic targeting of the complex has led to the development of monoclonal antibodies like nemolizumab, which inhibits IL-31RA, and vixarelimab, which targets OSMRβ [19, 25]. These drugs effectively disrupt the itch-scratch cycle by blocking the transmission of pruritic signals and reducing local skin inflammation [9, 20].

Other names

IL-31 receptorIL-31RIL-31RA/OSMRβ heterodimerGPL/OSMRβ complexInterleukin-31 receptor heterodimer

The complex functions as a heterodimeric receptor for IL-31 [1, 2]. Drugs like nemolizumab bind to the IL-31RA subunit to prevent IL-31 from initiating the signaling cascade [20, 25]. Vixarelimab targets the OSMRβ subunit, which is a shared component for both IL-31 and Oncostatin M (OSM) signaling, thereby providing dual inhibition of these pathways [19, 26]. Intracellularly, the complex signals through the JAK/STAT (Janus kinase/signal transducer and activator of transcription), PI3K/AKT, and MAPK pathways to mediate inflammation and pruritus [5, 39].