Evolution of Th2 responses: characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Stocchi, V.; Wang, Tiehui; Randelli, Elisa; Mazzini, Massimo; Gerdol, Marco; Pallavicini, Alberto; Scapigliati, Giuseppe; Buonocore, Francesco

doi:10.1038/s41598-017-02472-y

Cited by 26 publications

(12 citation statements)

References 48 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the existence of different isoforms for duplicated genes, so common in teleosts [ 73 ], was not detected with the current genomic data, but should not be discarded until more information is available. For instance, in the evolutionarily close European sea bass, two il4/13a isoforms have been described [ 74 ], and our preliminary analyses point to a similar event in gilthead sea bream that requires further study. The development of specific antibodies is also crucial to precisely define cell subtypes and functionally characterize them.…”

Section: Discussionmentioning

confidence: 72%

Hints on T cell responses in a fish-parasite model: Enteromyxum leei induces differential expression of T cell signature molecules depending on the organ and the infection status

et al. 2018

View full text Add to dashboard Cite

BackgroudEnteromyxum leei is a myxozoan parasite that produces a slow-progressing intestinal disease. This parasite invades the paracellular space of the intestinal epithelium and progresses from the posterior to the anterior intestine. The aim of the present study was to gain insights into fish T cell responses in the gilthead sea bream-E. leei infection model using a PCR-array with 30 signature molecules for different leukocyte responses in head kidney, spleen, anterior and posterior intestine.ResultsThe PCR-array results suggest that E. leei induced migration of T cells from head kidney to intestines where TH1, CTL and TH17 profiles were activated and kept in balance by the upregulation of regulatory cytokines. These results were partially validated by the use of cross-reacting antibodies and BrdU immunostaining to monitor proliferation. Zap70 immunostaining supported the increased number of T cells in the anterior intestine detected by gene expression, but double staining with BrdU did not show active proliferation of this cell type at a local level, supporting the migration from lymphohaematopoietic tissues to the site of infection. Global analyses of the expression profiles revealed a clear separation between infected and exposed, but non-infected fish, more evident in the target organ. Exposed, non-infected animals showed an intermediate phenotype closer to the control fish.ConclusionsThese results evidence a clear modulation of the T cell response of gilthead sea bream upon E. leei infection. The effects occurred both at local and systemic levels, but the response was stronger and more specific at the site of infection, the intestine. Altogether, this research poses a promising basis to understand the response against this important parasite and establish effective preventive or palliative measures.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3007-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 72%

Hints on T cell responses in a fish-parasite model: Enteromyxum leei induces differential expression of T cell signature molecules depending on the organ and the infection status

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Paralogs of IL-4Rα, IL-13Rα1 and IL-13Rα2 have also been identified in teleosts ( 316 , 317 ), while the recombinant fish IL-4/13A induces B and T cell expansion in an IL-13Rα-dependent manner ( 318 , 319 ), suggesting that the roles of these fish cytokines possess the immune roles of their mammalian counterparts. The fish IL-4/13A and IL-4/13B are thought to play the M2/anti-inflammatory roles attributed to the mammalian IL-4 and IL-13 ( 320 ) and the trout, seabass, grass carp and goldfish recombinant IL-4/13A and IL-4/13B possess many of these anti-inflammatory roles including the upregulation of immunosuppressive genes (TGF-β, IL-10, SAP1, and SOCS3); dampening of pro-inflammatory cytokine gene expression (TNFα, IL-1β, and IFNγ); as well as elevating macrophage/kidney phagocyte arginase gene expression and arginase activity ( 321 – 324 ). Notably, a true Th2 locus has been identified in spotted gar, consisting of RAD50, IL-4/13 and IL-3/IL-5/GM-CSF (IL-5) ( 325 ) while the constitutively high expression of trout and salmon IL4/13A in the thymus, skin and gill tissues have been attributed to immunological tolerance and thus a Th2-like response ( 320 ).…”

Section: Activation Of Alternative/m2 Teleost Macrophagesmentioning

confidence: 99%

Mechanisms of Fish Macrophage Antimicrobial Immunity

et al. 2018

View full text Add to dashboard Cite

Overcrowding conditions and temperatures shifts regularly manifest in large-scale infections of farmed fish, resulting in economic losses for the global aquaculture industries. Increased understanding of the functional mechanisms of fish antimicrobial host defenses is an important step forward in prevention of pathogen-induced morbidity and mortality in aquaculture setting. Like other vertebrates, macrophage-lineage cells are integral to fish immune responses and for this reason, much of the recent fish immunology research has focused on fish macrophage biology. These studies have revealed notable similarities as well as striking differences in the molecular strategies by which fish and higher vertebrates control their respective macrophage polarization and functionality. In this review, we address the current understanding of the biological mechanisms of teleost macrophage functional heterogeneity and immunity, focusing on the key cytokine regulators that control fish macrophage development and their antimicrobial armamentarium.

show abstract

“…Indeed, only 16 and 28 amino acids remained in the truncated IL-4/13A and IL-4/13B proteins, respectively (Figure 1H). Previous analysis of zebrafish protein sequences revealed conservation of an arginine in the αC helix (36) which is critical for the binding of human IL-4 to the IL-4Rα receptor. The mutations identified in IL-4/13A and IL-4/13B proteins abolished this residue implying that the proteins should not be able to bind to their receptors and thus lack any functional activity.…”

Section: Resultsmentioning

confidence: 99%

Zebrafish IL-4-like cytokines and IL-10 suppress inflammation but only IL-10 is essential for gill homeostasis

Bottiglione

Dee

Lea

et al. 2020

Preprint

View full text Add to dashboard Cite

26Healthy fish stocks are central to global food security. Key to fish health is robust 27 immunity at mucosal surfaces, and especially at the gills. However, a balance must be 28 struck between tolerating commensal microorganisms and reacting appropriately 29 toward pathogens. In mammals, IL-4 and IL-13 in concert with IL-10 are essential 30 for balancing immune response to pathogens and suppressing inflammation. Whether 31 their fish counterparts perform similar roles is an open question. Here, we have 32 generated IL-4/13A and IL-4/13B mutant zebrafish and, together with existing IL-10 33 mutants, characterized the consequences of loss-of-function of these cytokines. We 34 demonstrate that these cytokines are required to suppress inflammation. Further, IL-35 4/13A and IL-4/13B are required for the maintenance of a Th2-like phenotype in the 36 gills. As in mammals, IL-10 appears to have a more striking anti-inflammatory 37 function than IL-4-like cytokines. Thus, both IL-10 and IL-4/13 paralogues in 38 zebrafish exhibit aspects of conserved function with their mammalian counterparts. 39 40 42cytokines that participate in several physiological processes but are mainly known for 43 stimulating type 2 immune responses (1), characterised by mucus overproduction, IgE 44 antibody production, eosinophilia and differentiation of alternatively activated (M2) 45 macrophages (2). These responses confer protection against parasites but, when 46 inappropriately activated, contribute to the development of asthma and allergic 47 inflammation (1). IL-4 and IL-13 are secreted by CD4 + Th2 cells, basophils, 48 eosinophils, mast cells and group 2 innate lymphoid cells (ILC2s) (3). They exert 49 their functions by binding to two types of receptor complexes: a type I receptor, 50 3 constituted by the IL-4Rα chain and the IL-2R common γ chain (γc) and a type II 51 receptor, which comprises IL-4Rα chain and IL-13Rα1 subunits. Both type I and type 52 II receptors signal through STAT6 transcription factor binding to promoter elements 53 within IL-4/IL-13 responsive genes (4). IL-4 and IL-13 suppress inflammatory 54 responses by antagonising production of TNFα, IL-1β and other pro-inflammatory 55 mediators (5) and act in opposition to IFN-γ, the canonical Th1 (type 1) cytokine (6). 56Indeed, co-ordinately with inducing type 2 immune response, IL-4 and IL-13 suppress 57 type 1 responses, characterised by immune cell mediated destruction of cells infected 58 with intracellular pathogens (7). 59Although IL-4 and IL-13 can negatively regulate inflammatory responses, IL-60 10 has the more central anti-inflammatory role in mammals, potently suppressing 61 IFN-γ responses. IL-10 can suppress a range of aberrant immune responses including 62 both type 1 and type 2 responses (8). IL-10 is produced by many cell types (9). It 63 regulates CD4 + Treg cell differentiation and function, and it is important in 64 maintaining homeostasis at mucosal surfaces (10). 65Evidence is emerging that fish immune responses can also be classified as 66 type 1 or t...

show abstract

Evolution of Th2 responses: characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Cited by 26 publications

References 48 publications

Hints on T cell responses in a fish-parasite model: Enteromyxum leei induces differential expression of T cell signature molecules depending on the organ and the infection status

Hints on T cell responses in a fish-parasite model: Enteromyxum leei induces differential expression of T cell signature molecules depending on the organ and the infection status

Mechanisms of Fish Macrophage Antimicrobial Immunity

Zebrafish IL-4-like cytokines and IL-10 suppress inflammation but only IL-10 is essential for gill homeostasis

Contact Info

Product

Resources

About