Solene Gatault

Les polynucléaires éosinophiles sont des leucocytes multifonctionnels qui participent aux réponses innées et adaptatives par l’expression et la sécrétion de nombreux récepteurs et médiateurs. De plus en plus d’études, épidémiologiques, in vivo ou in vitro, suggèrent la participation des éosinophiles dans l’immunité anti-tumorale, et notamment dans le contexte du cancer du côlon. En effet, la présence d’une TATE (Tumor-Associated Tissue Eosinophilia) chez les sujets atteints de cancers est, en général, associée à un pronostic favorable. De même, notre laboratoire ainsi que d’autres équipes ont montré que les éosinophiles humains expriment des récepteurs et médiateurs, communs aux lymphocytes et connus pour être impliqués dans l’immunité anti-tumorale, tels que le 2B4, le complexe CD3/TCRγδ ou le granzyme A. La stimulation des éosinophiles in vitro, via ces récepteurs, conduit à la mort de cellules cancéreuses. Cet effet nécessitant un contact entre les cellules impliquant LFA-1 sur les éosinophiles. L’interleukine-18 est un membre de la famille des cytokines de l’IL-1. Elle fut initialement identifiée comme un facteur induisant la production d’IFNγ, basé sur sa capacité à promouvoir une réponse de type Th1 chez les lymphocytes et les cellules NK. Aujourd’hui, l’IL-18 est considérée comme une cytokine immuno-régulatrice capable de stimuler de nombreux types cellulaires. Son implication dans la réponse anti-tumorale est de plus en plus reconnue, notamment en favorisant la cytotoxicité de cellules NK. Nous avons donc étudié si cette cytokine pouvait également être impliquée dans la cytotoxicité des éosinophiles. Dans ce travail, nous avons démontré que les éosinophiles humains exercent une cytotoxicité vis-à-vis de plusieurs lignées cellulaires tumorales avec cependant une certaine hétérogénéité. L’IL-18 est non seulement capable d’activer in vitro les éosinophiles mais elle participe également à leur activité anti-tumorale vis-à-vis d’une lignée de carcinome du côlon, en favorisant notamment le contact entre les deux types cellulaires. Nos résultats proposent l’IL-18 comme un nouveau médiateur dans l'activité anti-tumorale des éosinophiles et apportent également un nouvel argument en faveur du rôle bénéfique que les éosinophiles peuvent exercer, notamment dans le contexte du cancer du colon.

We read this paper by Elise Tonoli et al. with interest, and we refer to its Discussion section where three modes of inheritance were proposed for Olmsted syndrome [1]. These were autosomal dominant, X-linked dominant, and X-linked recessive. The X-linked mode of inheritance has been questioned due to recent advancements in and ease of sequencing. We highlight the discrepancies and discuss the literature to date on this issue as follows.

Demodex mites are microscopic arachnids found in the normal skin of many mammals. In humans, it is well established that Demodex mite density is higher in patients with the skin condition rosacea, and treatment with acaricidal agents is effective in resolving symptoms. However, pathophysiology of rosacea is complex and multifactorial. In dogs, demodicosis is a significant veterinary issue, particularly the generalized form of the disease which can be fatal if untreated. In each species, clinical and molecular studies have shown that the host’s immunological interactions with Demodex mites are an important, but not fully understood, aspect of how Demodex can live in the skin either as a harmless commensal organism or as a pathogenic agent. This review outlines the role of Demodex mites in humans and dogs, considering morphology, prevalence, symptoms, diagnosis, histology treatment and pathogenesis.

Molecular cross‐talk between the immune system and the nervous system elicit evolutionary responses such as itch (pruritus) to protect the host from potential pathogens ^1,2. This neuroimmune, physiological response serves notably to remove pathogens from the skin ¹. Pruritus can also be associated with inflammatory disorders such as atopic dermatitis (AD) ³. Indeed, AD is a common skin disease in which IL‐4 and IL‐13 are key players in inflammation and neuroimmune dysfunction.

Background Atopic Dermatitis (AD) is a complex skin disease involving causative effects from both intrinsic and extrinsic sources. Murine models of the disease often fall short in one of these components and as a result, do not fully encapsulate these disease mechanisms. Objective We aimed to determine whether the protease‐activated receptor 2 over‐expressor mouse (PAR2OE) with topical house dust mite (HDM) application is a more comprehensive and clinically representative AD model. Methods Following HDM extract application to PAR2OE mice and controls, AD clinical scoring, itching behaviour, skin morphology and structure, barrier function, immune cell infiltration and inflammatory markers were assessed. Skin morphology was analysed using haematoxylin and eosin staining and barrier function was assessed by transepidermal water loss measurements. Immune infiltrate was characterised by histological and immunofluorescence staining. Finally, an assessment of AD‐related gene expression was performed using quantitative RT‐PCR. Results PAR2OE mice treated with HDM displays all the characteristic clinical symptoms including erythema, dryness and oedema, skin morphology, itch and inflammation typically seen in AD patients. There is a significant influx of mast cells (p<0.01) and eosinophils (p<0.0001) into the dermis of these mice. Furthermore, the PAR2OE + HDM mice exhibit similar expression patterns of key differentially expressed genes as seen in human AD. Conclusion The PAR2OE + HDM mouse presents with a classic AD pathophysiology and is a valuable model in terms of reproducibility and overall disease representation to study the condition and potential therapeutic approaches.

Demodex mites have been suggested to have a role in various cutaneous and ocular disorders pathogenesis, such as rosacea or blepharitis. Evaluation of potential treatments with anti-Demodex effects is difficult because the viability of living mites needs to be evaluated during their exposure to the agent being tested. Mite viability is currently based solely on their observed movement. However, this method of assessing viability has significant limitations as mites may be resting, immobile or paralysed at any given observation point giving the observer a false impression of the organism’s death. To overcome this limitation we evaluated a new quantitative method of evaluating the viability of Demodex mites by using scattered light intensity (SLI). We demonstrated that when combined with observation of mite motility, SLI provided increased accuracy of the evaluation of viability of mites being studied. This new viability assay will help address the technical challenges of mite viability experiments. Accurate evaluation of mite viability will enhance mite biology research and allow for more accurate in vitro toxicity assays of proposed anti-mite agents.

P28GST, a 28Kd glutathione S-transferase enzymatic protein derived from a schistosome helminth prevents experimental colitis when administered subcutaneously in the presence of adjuvant by decreasing pro-inflammatory Th1/Th17 response. Given the antioxidant properties of P28GST, we evaluated its anti-inflammatory potential when administered locally after colitis induction in the absence of adjuvant. Colitis was induced in BALB/c mice by rectal administration of TNBS, followed by two intraperitoneal injections of P28GST at day 1 and day 2. Mice were sacrificed 48h after TNBS administration and evaluated for macroscopic and histological scores, myeloperoxidase (MPO) quantification and cytokine messenger RNA expression in the colonic tissues. Both clinical and histological scores significantly decreased in mice treated with P28GST at 5 or 50μg/kg when compared to vehicle- treated mice. A significant reduction of MPO was detected in colonic tissues from P28GST–treated mice, similarly to mice treated with methylprednisolone as the reference treatment. Pro-inflammatory cytokines TNF, IL-1β, and IL-6, mRNA as well as serum levels were down-regulated in mice colonic tissues treated with P28GST at 5 or 50μg/kg. In addition, a significant decrease of mRNA expression levels of T-bet, and ROR-γ, respective markers of Th1 and Th17 cells was observed. Whereas no significant effect was detected on Gata3 mRNA, a marker of Th2 cells, the Arg/iNOS mRNA levels significantly increased in P28GST-treated mice, suggesting the induction of M2 macrophages. These findings provide evidence that P28GST injected locally after colitis induction induces a potent decrease of colitis inflammation in mice, associated to downregulation of Th1/Th17 response, and induction of anti-inflammatory alternatively activated macrophages.