Psoriasis is a common chronic autoimmune condition of the skin characterized by hyperplasia of epidermal keratinocytes associated with pro-inflammatory cytokines. IL-33 is a new member of the IL-1 superfamily that signals through the ST2 receptor and was originally defined as an inducer of T helper 2 (Th2) cytokines. Recently, broader immune activatory potential has been defined for IL-33 particularly via mast cell activation and neutrophil migration. Here, we show that ST2 À/À mice exhibit reduced cutaneous inflammatory responses compared with WT mice in a phorbol ester-induced model of skin inflammation. Furthermore, injections of IL-33 into the ears of mice induce an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell-deficient mice (Kit W-sh/W-sh ) showed delayed responses to IL-33. IL-33 also recruited neutrophils to the ear, an effect mediated in part by increased production of the chemokine KC (CXCL1). Finally, we show that IL-33 expression is up-regulated in the epidermis of clinical psoriatic lesions, compared with healthy skin. These results therefore demonstrate that IL-33 may play a role in psoriasis-like plaque inflammation. IL-33 targeting may provide a new treatment strategy for psoriasis.

Infections with pinworms are common in rodent animal facilities. In this study, we show the consequence of an outbreak in a transgenic barrier facility of infection by Syphacia obvelata, a murine pinworm gastrointestinal nematode. Immune responses were defined in experimental infection studies with BALB/c mice. Infection with S. obvelata induced a transient Th2-type immune response with elevated interleukin 4 (IL-4), IL-5, and IL-13 cytokine production and parasite-specific immunoglobulin G1 (IgG1). In contrast, BALB/c mice deficient in IL-13, IL-4/13, or the IL-4 receptor alpha chain showed chronic disease, with a >100-fold higher parasite burden, increased gamma interferon production, parasite-specific IgG2b, and a default Th2 response. Interestingly, infected IL-4 ؊/؊ BALB/c mice showed only slightly elevated parasite burdens compared to the control mice, suggesting that IL-13 plays the dominant role in the control of S. obvelata. The influence that pinworm infection has on the allergic response to a dietary antigen was found to be important. Helminth-infected mice immunized against ovalbumin (Ova) elicited more severe anaphylactic shock with reduced Ova-specific IL-4 and IL-5 than did noninfected controls, demonstrating that S. obvelata infection is able to influence nonrelated laboratory experiments. The latter outcome highlights the importance of maintaining mice for use as experimental models under pinworm-free conditions.

Background: Intestinal mucus production by hyperplasic goblet cells is a striking pathological feature of many parasitic helminth infections and is related to intestinal protection and worm expulsion. Induction of goblet cell hyperplasia is associated with TH2 immune responses, which in helminth infections are controlled primarily by IL-13, and also IL-4. In the study presented here we examine the goblet cell hyperplasic response to three experimental parasitic helminth infections; namely Nippostrongylus brasiliensis, Syphacia obvelata and Schistosoma mansoni.

Summary The T helper type 2 (Th2) mediated expulsion of the gastrointestinal nematode Trichinella spiralis requires interleukin‐4 receptor α (IL‐4Rα) expression on both bone‐marrow‐derived and non‐bone‐marrow‐derived cells. To more definitively investigate the role of IL‐4/IL‐13 responsiveness in the development of protective immunity to T. spiralis, cell‐specific IL‐4Rα signalling on CD4+ T cells (Lckcre IL‐4Rα−/flox) and macrophages/neutrophils (LysMcre IL‐4Rα−/flox) was analysed on the BALB/c background. Infection of wild‐type and control IL‐4Rα−/flox mice induced a Th2‐type immune response with elevated IL‐4 cytokine production, parasite‐specific immunoglobulin G1 (IgG1), total IgE, intestinal mastocytosis and enteropathy. In contrast, global IL‐4Rα‐deficient BALB/c mice showed reduced worm expulsion, antibody production, intestinal mastocytosis and gut pathology. BALB/c mice generated with cell‐specific deletion of IL‐4Rα on CD4+ T lymphocytes or macrophages/neutrophils, controlled gastrointestinal helminth infection by eliciting a protective immune response comparable to that observed with wild‐type and IL‐4Rα−/flox controls. Together, this shows that the development of host protective Th2 responses accompanied by parasite loss is independent of IL‐4Rα expression on CD4+ T cells and macrophages/neutrophils.