Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

Abstract

BackgroundThe role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized.MethodsThe response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients.ResultsHDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient’s pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset.ConclusionIgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

CLA+ memory T cells in atopic dermatitis

“…The IL‐31 response positively correlated with CCL27 plasma levels too (Figure 3), which is supported by the fact that stratum corneum CCL27 constitutes a biomarker of response to nemolizumab 114 . Additionally, it was suggested that plasma levels of HDM‐specific IgE may stratify moderate‐to‐severe AD patients and hopefully be useful for identifying patients more probable to be responders for IL‐31‐directed therapies 111 . Interestingly, patients with elevated IgE levels (>1000 kU/L) display increased expression of IL‐31RA on memory B cells, 115 supporting the association between IL‐31 and IgE sensitization.…”

“…114 Additionally, it was suggested that plasma levels of HDM-specific IgE may stratify moderate-to-severe AD patients and hopefully be useful for identifying patients more probable to be responders for IL-31-directed therapies. 111 Interestingly, patients with elevated IgE levels (>1000 kU/L) display increased expression of IL-31RA on memory B cells, 115 supporting the association between IL-31 and IgE sensitization.…”

“…108 CLA + T reg population from AD patients also express increased levels of OX40 compared to healthy controls and correlates with disease severity. 109,110 IL-31 is a neuroimmune cytokine that was originally described as mainly produced by CLA + memory Th2 cells in AD, 64,111,112 with implications in pruritus, inflammation, fibrosis and epidermal barrier dysfunction. 113 Although there is an anti-IL31RA Mab (nemolizumab) in phase III for AD, the production of IL-31 and its relationship with the clinical status of the patients has not been characterized.…”

CLA + memory T cells in atopic dermatitis

“…Additionally, it was suggested that plasma levels of HDM-specific IgE may stratify moderate-to-severe AD patients and hopefully be useful for identifying patients more probable to be responders for IL-31-directed therapies. 96 Supported by proteomic 97 and transcriptomic studies, 98 as well as, differentiated responses to Th2-targeted therapies, and similarly to asthma, Th2 high and Th2 low endotypes have been hypothesized. A recent coculture model defined the SEB-CLA + memory T-cell-IL-13 axis to functionally distinguish Th2 high and Th2 low responders within a clinically homogeneous adult moderate-to-severe AD population.…”