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Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Co-incident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intra-tumoural innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the cross-talk between allergic response and cancer is paving the way for new avenues of treatment.

Persistent and relapsing itch commonly manifests in inflammatory skin disorders such as atopic dermatitis (AD). AD pathogenesis is driven by interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13). Dupilumab, a monoclonal antibody blocking the action of IL‐4 and IL‐13 effectively reduces the symptoms of AD and itch. Little is known whether IL‐4 and IL‐13 directly contribute to itch transduction. A recently published study (Oetjen et al, Cell, 2017, 171, 217) found IL‐4 and IL‐13 to directly activate itch‐sensory neurons in vitro. Surprisingly, they found no significant increase in scratching after intradermally injecting high doses (2.5 ug/ml) of IL‐4 and IL‐13 into mice. Similar experiments in our lab, however, suggested that both IL‐4 and IL‐13 contribute to acute itch in vivo. We intradermally injected lower doses (1 ug/ml) of IL‐4 and IL‐13 into mice and found a significant increase of scratching bouts compared to vehicle. Interestingly, the combined treatment of IL‐4 and IL‐13 produced additive increase of scratching and acute pruritus at an earlier time point compared to each cytokine administered alone. In summary, our study shows a rapid and significant increase of scratching after intradermal injection of IL‐4, IL‐13 or combined IL‐4/ IL‐13 compared to vehicle in mice 5‐10 minutes after injection. Our data suggest that IL‐4 and IL‐13 alone and combined directly act as potent acute pruritogens on sensory nerves. This finding expands our understanding of cytokines as pruritogens, how targeted anticytokine medications act in AD, and about neuroimmune communication in the skin.

Eosinophils are multifunctional leukocytes that are involved in innate and adaptive immune responses through the expression of various receptors and mediators. Previously, we showed that human eosinophils and T cells shared cytotoxic activities against tumor cells that involved the γ-δ TCR and cell–cell contact. In this study, we investigated the molecules involved in eosinophil–tumor cell interactions. Given the role of IL-18 in cell adhesion and in protecting against colon cancer, we evaluated its role in eosinophil-mediated cytotoxicity against Colo-205, a human colon carcinoma cell line. We found that human eosinophils exerted dose- and time-dependent tumoricidal activity against Colo-205 cells. Neutralization of IL-18 significantly reduced eosinophil-mediated Colo-205 apoptosis and inhibited cell–cell adhesion. Moreover, addition of rIL-18 led to upregulation of CD11a and ICAM-1 adhesion molecules, which were involved in the contact between eosinophils and Colo-205 cells. Our results indicated that IL-18 was involved in the eosinophil-mediated death of Colo-205 by facilitating contact between effector and target cells. These data underscored the involvement of an additional mediator in eosinophil-mediated antitumor cytotoxicity. Our findings support existing evidence that eosinophils could play a beneficial role in the context of colon cancer.

Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases.

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.

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 overexpressor 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 patients with AD. There is a significant influx of mast cells (P < .01) and eosinophils (P < .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.

BackgroundP28GST, 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.MethodsColitis 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.ResultsBoth 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.ConclusionsThese 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.