Interleukin-17A (IL-17A), the hallmark cytokine of the newly defined T helper 17 (T(H)17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease. IL-17A and its receptor (IL-17RA) are the founding members of a newly described family of cytokines and receptors that have unique structural features which distinguish them from other cytokine families. Research defining the signal transduction pathways induced by IL-17R family cytokines has lagged behind that of other cytokine families, but studies in the past 2 years have begun to delineate unusual functional motifs and new proximal signalling mediators used by the IL-17R family to mediate downstream events.

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Structure and signalling in the IL-17 receptor family.

Innate lymphoid cells (ILCs) are newly identified members of the lymphoid lineage that have emerging roles in mediating immune responses and in regulating tissue homeostasis and inflammation. Here, we review the developmental relationships between the various ILC lineages that have been identified to date and summarize their functions in protective immunity to infection and their pathological roles in allergic and autoimmune diseases.

Innate lymphoid cells — how did we miss them?

Advancing our understanding of mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T(h) and regulatory T cells, as well as subsets of B cells, offer opportunities for immune interventions. Here, we review current knowledge about ILs 1 to 37 and IFN-γ. Our understanding of the effects of ILs has greatly increased since the discoveries of monocyte IL (called IL-1) and lymphocyte IL (called IL-2); more than 40 cytokines are now designated as ILs. Studies of transgenic or knockout mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided important information about IL and IFN functions. We discuss their signaling pathways, cellular sources, targets, roles in immune regulation and cellular networks, roles in allergy and asthma, and roles in defense against infections.

https://www.jacionline.org/article/S0091-6749(10)01949-4/pdf

Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases

All metazoans possess innate immune defence system whereas parameters of the adaptive immune system make their first appearance in the gnathostomata, the jawed vertebrates. Fish are therefore the first animal phyla to possess both an innate and adaptive immune system making them very interesting as regards developmental studies of the immune system. The massive increase in aquaculture in recent decades has also put greater emphasis on studies of the fish immune system and defence against diseases commonly associated with intensive fish rearing. Some of the main components of the innate and adaptive immune system of fish are described. The innate parameters are at the forefront of immune defence in fish and are a crucial factor in disease resistance. The adaptive response of fish is commonly delayed but is essential for lasting immunity and a key factor in successful vaccination. Some of the inherent and external factors that can manipulate the immune system of fish are discussed, the main fish diseases are listed and the pathogenicity and host defence discussed. The main prophylactic measures are covered, including vaccination, probiotics and immunostimulation. A key element in the immunological control of fish diseases is the great variation in disease susceptibility and immune defence of different fish species, a reflection of the extended time the present day teleosts have been separated in evolution. Future research will probably make use of molecular and proteomic tools both to study important elements in immune defence and prophylactic measures and to assist with breeding programmes for disease resistance.

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Immunological Control of Fish Diseases

Iconographies supplémentaires de l'article : Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases

Among lectins in the skin mucus of fish, primary structures of four different types of lectin have been determined. Congerin from the conger eel Conger myriaster and AJL-1 from the Japanese eel Anguilla japonica were identified as galectin, characterized by its specific binding to beta-galactoside. Eel has additionally a unique lectin, AJL-2, which has a highly conserved sequence of C-type lectins but displays Ca(2+)-independent activity. This is rational because the lectin exerts its function on the cutaneous surface, which is exposed to a Ca(2+) scarce environment when the eel is in fresh water. The third type lectin is pufflectin, a mannose specific lectin in the skin mucus of pufferfish Takifugu rubripes. This lectin showed no sequence similarity with any known animal lectins but, surprisingly, shares sequence homology with mannose-binding lectins of monocotyledonous plants. The fourth lectin was found in the ponyfish Leiognathus nuchalis and exhibits homology with rhamnose-binding lectins known in eggs of some fish species. These lectins, except ponyfish lectin, showed agglutination of certain bacteria. In addition, pufflectin was found to bind to a parasitic trematode, Heterobothrium okamotoi. Taken together, these results demonstrate that skin mucus lectins in fish have wide molecular diversity.

Molecular diversity of skin mucus lectins in fish.

Lectins Homologous to Those of Monocotyledonous Plants in the Skin Mucus and Intestine of Pufferfish, Fugu rubripes

The characteristics and primary structure of AJL-1, one of the lectins in the skin mucus of the Japanese eel (Anguilla japonica), were examined. This lectin exhibited beta-galactoside specific activity in a Ca2+ independent manner. We previously reported that its molecular mass was 16,091Da, although it was approximately 30 kDa as determined by gel filtration, indicating that it is a homodimer having non-covalent bonds. This lectin was composed of 142 amino acid residues having no half-cystinyl residues, and showed homology to members of the galectin family, especially to proto-type galectins. Gene expression of this lectin was detected in skin only, and relative expression was high in an individual that exhibited resistance to infectious disease. AJL-1 showed agglutinating activity against pathogenic bacteria, Streptococcus difficile. This suggests that AJL-1 functions as an important defensive factor at the body surface.

Characteristics and primary structure of a galectin in the skin mucus of the Japanese eel, Anguilla japonica.

Yeast-binding C-type lectin with opsonic activity from conger eel (Conger myriaster) skin mucus.

To determine whether fish intestinal epithelial cells (IECs) contribute to mucosal immunity, we established a method for isolating IECs from the rainbow trout Oncorhynchus mykiss and examined cytokine production in these cells. Components of the intestinal epithelium were released by incubation of intestinal pieces with 1 mM dithiothreitol (DTT)/ethylenediamine tetraacetic acid (EDTA). The IEC-rich fraction (purity >90%; survival rate ∼95%) was obtained by centrifugation on a 35%/40% Percoll gradient, followed by magnetic cell sorting using an anti-trout IgM antiserum. The gene expression profiles of 14 cytokines in trout IECs were investigated after culturing the cells for 6 h with or without the pathogenic bacterium Aeromonas salmonicida . Trout IECs could produce several cytokines, of which IL-1β and TNFα2 were upregulated when the cells were stimulated with live A. salmonicida . Immunohistochemical analyses with the anti-trout TNF antibody confirmed that the TNF protein was present in the IECs of trout that were intra-anally challenged with live A. salmonicida . These results show that trout IECs are an important trigger of the intestinal immune system. Further, formalin-killed A. salmonicida , conditioned medium of this bacterium, or live nonpathogenic Escherichia coli could not upregulate the expression of these cytokines. These results indicate that the production of inflammatory cytokines by IECs is caused by the adhesion of A. salmonicida , but is not due to only simple ligand–receptor interactions between the surface molecules of IECs and the bacterium or in response to bacterial secretions.

Shigeyuki Tsutsui

Papers

Molecular diversity of skin mucus lectins in fish.

Lectins Homologous to Those of Monocotyledonous Plants in the Skin Mucus and Intestine of Pufferfish, Fugu rubripes

Characteristics and primary structure of a galectin in the skin mucus of the Japanese eel, Anguilla japonica.

Yeast-binding C-type lectin with opsonic activity from conger eel (Conger myriaster) skin mucus.

Expression profiles of cytokines released in intestinal epithelial cells of the rainbow trout, Oncorhynchus mykiss, in response to bacterial infection