Manuela Gehring

IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis

To cite this article: Raap U, Weißmantel S, Gehring M, Eisenberg AM, Kapp A, Fölster‐Holst R. IL‐31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis. Pediatr Allergy Immunol 2012: 23: 285–288.

Increased levels of serum IL-31 in chronic spontaneous urticaria*

Please cite this paper as: Increased levels of serum IL‐31 in chronic spontaneous urticaria. Experimental Dermatology 2010; 19: 464–466.

Modulation of basophil activity: A novel function of the neuropeptide α-melanocyte–stimulating hormone

BACKGROUND Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses. OBJECTIVE This study aimed at revealing the role of α-melanocyte-stimulating hormone (α-MSH) on basophil function. METHODS Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, Western immunoblotting, fluorescence-activated cell sorting, and double-immunofluorescence analysis. Signal transduction studies included cyclic AMP and Ca(2+) mobilization assays. Basophil activity was assessed based on CD63 surface expression and cytokine release. RESULTS MC-1R expression was detectable in basophils isolated from human peripheral blood, as well as in basophils within nasal tissue. In isolated basophils from human blood, truncated POMC transcripts were present, but there was no POMC protein. Treatment of basophils with α-MSH increased intracellular Ca(2+) but not cyclic AMP levels. α-MSH at physiologic doses potently suppressed basophil activation induced by N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or grass pollen allergen in whole blood of healthy or allergic subjects, respectively. The effect of α-MSH on basophil activation was MC-1R mediated (as shown by blockade with a peptide analogue of agouti-signaling protein) and imitated by adrenocorticotropic hormone but not elicited by the tripeptides KPV and KdPT, both of which lack the central pharmacophore of α-MSH. Moreover, α-MSH at physiologic doses significantly suppressed secretion of 3 proallergic cytokines, IL-4, IL-6, and IL-13, in basophils stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenylalanine, or phorbol 12-myristate 13-acetate. CONCLUSION Our findings highlight a novel functional activity of α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

Human Basophils are Differentially Activated by and are a Source of IL-31

Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL‐31 serum levels. So far the effects of IL‐31 on human basophils are unknown.

Human basophil chemotaxis and activation are regulated via the histamine H4 receptor.

IgE‐mediated cross‐linking of FcεRI results in the release of mediators stored in basophil granules, such as histamine and proteases, and in the de novo synthesis of sulfidoleukotrienes.

Substance P activates human eosinophils.

Substance P activates human eosinophils Mieke Raap, Urda R€ udrich, Sonja St€ ander, Manuela Gehring, Alexander Kapp and Ulrike Raap Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Department of Dermatology, University Hospital of M€ unster, Hannover, Germany Correspondence: Prof Dr med. Ulrike Raap, Department of Dermatology and Allergy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany, Tel.: 49-511-532-7675, Fax: 49-511-532-18854, e-mail: raap.ulrike@mh-hannover.de

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria

Background Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non‐allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear.

Childhood atopic dermatitis—Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity

Several studies have shown that neurotrophins including brain‐derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL‐4, IL‐13 and IL‐31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss‐of‐function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin‐positive or filaggrin‐negative children with AD, and there was no correlation of BDNF with IL‐31 and Th2 cytokines including IL‐4 and IL‐13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil‐, but not Th2‐dependent manner.

Eosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid

Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.