Characterization of skin Th17 transcriptional profiles in psoriatic patients under adalimumab biotherapy.

In psoriasis, a specific cytokine network has been described to play a central role in the pathophysiology of the disease. Anti-cytokine therapeutic approaches have been largely developed and TNFα constitutes the main target. Adalimumab is a human anti-TNFα monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation. We aimed to analyse changes in the skin inflammatory transcriptomic profile in psoriatic patients during adalimumab therapy. In addition, the circulating cytokine profile was analysed to define systemic inflammation. Eighteen patients with chronic plaque psoriasis were treated with adalimumab. After four and 16 weeks, clinical efficacy was assessed using PASI and DLQI, and skin mRNA profiles were determined and circulating cytokines quantified. We identified a rapid effect of adalimumab therapy on a large array of Th17 cytokines of the skin, which may account for the modification of keratinocyte expression profile and clinical response. In contrast, analysis of serum cytokine concentrations was uninformative, confirming the need for characterization of local cytokines in skin lesions. Finally, in non-responders, local cytokine expression was shown to be unchanged. We show that TNFα inhibition in psoriasis patients treated with adalimumab has a broad effect on the expression profile of cytokines and keratinocyte markers of skin inflammation, which may account for its clinical efficacy.

Study of proliferation and 3D epidermal reconstruction from foreskin, auricular and trunk keratinocytes in children.

OBJECTIVE: Severe burns in children are conventionally treated with split-thickness skin autografts or epidermal sheets. An alternative approach is to graft isolated keratinocytes. We evaluated foreskin and other anatomic sites as donor sources for autologous keratinocyte graft in children. We studied in vitro capacities of isolated keratinocytes to divide and reconstitute epidermal tissue. METHODS: Keratinocytes were isolated from foreskin, auricular skin, chest and abdominal skin by enzymatic digestion. Living cell recovery, in vitro proliferation, epidermal reconstruction capacities and differentiation status were analyzed. RESULTS: In vitro studies revealed the higher yield of living keratinocyte recovery from foreskin and higher potential in terms of proliferative capacity, regeneration and differentiation. Cultured keratinocytes from foreskin express lower amounts of differentiation markers than those isolated from trunk and ear. Histological analysis of reconstituted human epidermis derived from foreskin and inguinal keratinocytes showed a structured multilayered epithelium, whereas those obtained from ear pinna-derived keratinocytes were unstructured. CONCLUSION: Our studies highlight the potential of foreskin tissue for autograft applications in boys. A suitable alternative donor site for autologous cell transplantation in female paediatric burn patients remains an open question in our department. We tested the hypothesis that in vitro studies and RHE reconstructive capacities of cells from different body sites can be helpful to select an optimal site for keratinocyte isolation before considering graft protocols for girls.

IL-22, in contrast to IL-10, does not induce Ig production, due to absence of a functional IL-22 receptor on activated human B cells.

IL-22 is an IL-10 homologue that binds to and signals via the class II cytokine receptor (R) heterodimer IL-22RA1/CFR2-4 (IL-10R2), the latter chain being part of the IL-10R complex. Here, we report that, despite its structural similarity with IL-10, as well as its use of the common IL-10R2 chain, IL-22, in contrast to IL-10, is unable to induce Ig production by activated human B cells. Whereas culture of anti-CD40 mAb-stimulated splenic or tonsillar B cells in the presence of rIL-10 resulted in the production of IgG, IgG1, IgG3 and IgA, rIL-22, at concentrations ranging from 4 to 100 ng/ml, did not induce the production of any of these isotypes. Moreover, unlike rIL-10 which enhanced rIL-4-induced IgG4 and IgE production, rIL-22 was ineffective. Although activated B cells expressed transcripts for a soluble IL-22-binding protein (IL-22RA2), no mRNA for a transmembrane IL-22R (IL-22RA1) could be detected. The latter result was confirmed by the demonstration that rIL-22 failed to induce activation of STAT-3 and -5 in resting or activated B cells. Together, these data show that IL-22, in contrast to its homologue IL-10, is not involved in the immunological activity of B cells, which is due to the absence of a functional IL-22R at the surface of these cells.