Reduced IL‐31 receptor alpha splice variant mRNA following allergen challenge in a canine model of atopic dermatitis

Transcription of interleukin 31 and its receptor by leukocytes after Culicoides sp stimulation is dose dependent but is not exaggerated in allergic horses or correlated with pruritus

“…We have observed a similarly reduced transcription of both long and short IL-31RA splice variants in the skin of atopic dogs following stimulation of allergic inflammation by allergen challenge. 47 In this canine experimental model of AD, transcription of IL-31RA was reduced and negatively correlated with the severity of the dermatitis. If inhibitory IL-31RA splice variants account for the increased transcription in response to C nubeculosus, dysregulated or reduced transcription of these variants could be a factor in pruritus in the IBH group.…”

“…However, it is not currently known which other mRNA splice variants are present in horses, and these may include inhibitory, soluble, decoy, or nonfunctional IL-31RA splice variants, as have been identified in humans, dogs, and mice, which may also be detected by our qPCR assay. [43][44][45][46][47] As mentioned previously, IL-31 signaling has been shown to have a role in regulating Th2 inflammation in response to parasites, and IL-31RA splice variants may have a similar regulatory role in allergic inflammation, as suggested by the observation that IL-31RA-deficient mice produce stronger Th2 immune responses to Japanese cedar pollen allergen than wild-type mice. 37,38,48 Follow-up studies of STAT activation in response to IL-31 following C nubeculosus-induced upregulation of IL-31RA are needed to clarify whether this IL-31RA enhances or limits IL-31 sensitivity and how this influences our observations that there is no difference between normal and IBH horses and that IL-31RA does not correlate with IL-31 at the higher C nubeculosus dose.…”

Update on the role of cytokines and chemokines in canine atopic dermatitis

“…66 Although the transcription of IL-31RA X2 was significantly higher than that of IL-31RA X1 in both HDM-induced atopic and healthy dogs, the difference in the function between these isoforms remains to be confirmed. 66 As in humans and mice, several studies in dogs have described the expression of IL-31RA on dorsal root ganglia, where the cell bodies of cutaneous sensory neurons are located. [67][68][69][70][71] Expression of IL-31RA protein also has been demonstrated in nerve fibres in the skin of dogs with AD.…”

“…65 There are currently five mRNA splice variants of IL-31 receptor α subunit (IL-31RA) in dogs encoding two protein isoforms: the full-length isoform X1 and the truncated isoform X2. 66 The latter lacks the N-terminal signal peptide and parts of the cytokine-binding domain; therefore, it may not bind to IL-31. 66 Although the transcription of IL-31RA X2 was significantly higher than that of IL-31RA X1 in both HDM-induced atopic and healthy dogs, the difference in the function between these isoforms remains to be confirmed.…”

“…66 The latter lacks the N-terminal signal peptide and parts of the cytokine-binding domain; therefore, it may not bind to IL-31. 66 Although the transcription of IL-31RA X2 was significantly higher than that of IL-31RA X1 in both HDM-induced atopic and healthy dogs, the difference in the function between these isoforms remains to be confirmed. 66 As in humans and mice, several studies in dogs have described the expression of IL-31RA on dorsal root ganglia, where the cell bodies of cutaneous sensory neurons are located.…”