IL-4 Induces Characteristic Th2 Responses Even in the Combined Absence of IL-5, IL-9, and IL-13

Fallon, Padraic G.; Jolin, Helen E.; Smith, Philip; Emson, Claire; Townsend, Michael J.; Fallon, Rosie E.; McKenzie, Andrew N. J.

doi:10.1016/s1074-7613(02)00332-1

Cited by 315 publications

(240 citation statements)

References 40 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…It is important to note that although it is widely accepted that the IL‐13/IL‐4 signalling axis is the primary mediator of goblet cell hyperplasia, and therefore effector functions,49, 60, 61 there is evidence to suggest that other immune mediators can coordinate goblet cell effector functions. For example, a study conducted by Marillier and colleagues demonstrated goblet cell hyperplasia is observed independent of the IL‐13/IL‐4 signalling apparatus,62 and Muc2 and Muc3 transcripts were augmented even in the absence of IL‐4 during T. spiralis infection 50.…”

Section: Immune Control Against Gi Nematode Infectionmentioning

confidence: 99%

A sticky end for gastrointestinal helminths; the role of the mucus barrier

Sharpe

Thornton

Grencis

2018

Parasite Immunology

View full text Add to dashboard Cite

SummaryGastrointestinal (GI) nematodes are a group of successful multicellular parasites that have evolved to coexist within the intestinal niche of multiple species. It is estimated that over 10% of the world's population are chronically infected by GI nematodes, making this group of parasitic nematodes a major burden to global health. Despite the large number of affected individuals, there are few effective treatments to eradicate these infections. Research into GI nematode infections has primarily focused on defining the immunological and pathological consequences on host protection. One important but neglected aspect of host protection is mucus, and the concept that mucus is just a simple barrier is no longer tenable. In fact, mucus is a highly regulated and dynamic‐secreted matrix, underpinned by a physical hydrated network of highly glycosylated mucins, which is increasingly recognized to have a key protective role against GI nematode infections. Unravelling the complex interplay between mucins, the underlying epithelium and immune cells during infection are a major challenge and are required to fully define the protective role of the mucus barrier. This review summarizes the current state of knowledge on mucins and the mucus barrier during GI nematode infections, with particular focus on murine models of infection.

show abstract

Section: Immune Control Against Gi Nematode Infectionmentioning

confidence: 99%

A sticky end for gastrointestinal helminths; the role of the mucus barrier

Sharpe

Thornton

Grencis

2018

Parasite Immunology

View full text Add to dashboard Cite

show abstract

“…CBA/N (xid) and wild-type (CBA/Ca) mice were obtained from Harlan (Horst, The Netherlands), and age-matched male mice were used in experiments. IL-13 transgenic (13) and IL-4-(14), IL-5-(15), IL-9-(16), and IL-13-(17) deficient mice and combined IL-4-, IL-5-, IL-9-, and IL-13-deficient mice (15) were bred in-house. Mice were housed in a specific pathogen-free facility in individually ventilated and filtered cages under positive pressure (Techniplast, Northants, U.K.).…”

Section: Micementioning

confidence: 99%

“…To exclude a role for IL-4 and other Th2 cytokines (IL-5, IL-9, and IL-13) known to induce allergic responses, a B cell transfer experiment was performed with cells from multiknockout (mKO) mice that have a combined deficiency in IL-4, IL-5, IL-9, and IL-13 (15). B cells from mKO and wild-type mice were modulated with worms in vitro and transferred to Pen V-OVA-immunized mice before Pen V-BSA challenge and induction of anaphylaxis.…”

Section: Transfer Of In Vitro Worm-modulated Th2 Cytokine-deficient mentioning

confidence: 99%

Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Mangan

Fallon

Smith³

et al. 2004

The Journal of Immunology

Self Cite

246

208

View full text Add to dashboard Cite

Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses.

show abstract

“…Eosinophils, which play an important role in asthma, are recruited into the lung during both acute and chronic pulmonary inflammation (2,3). Accumulating evidence has demonstrated that the eosinophil infiltration into lungs both in animal models and human diseases can be attributed to the high expression of eotaxins (4,5), and increased IL-4 production is associated with eosinophilia and promotes eosinophilic inflammation through induction of eotaxin-1 (6,7).…”

mentioning

confidence: 99%

Upregulated Protein Arginine Methyltransferase 1 by IL-4 Increases Eotaxin-1 Expression in Airway Epithelial Cells and Participates in Antigen-Induced Pulmonary Inflammation in Rats

Sun

Yang

Zhong

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Protein arginine methyltransferases (PRMTs), catalyzing methylation of both histones and other cellular proteins, have emerged as key regulators of various cellular processes. This study aimed to identify key PRMTs involved in Ag-induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of PRMT1 in the IL-4–induced eosinophil infiltration process. E3 rats were i.p. sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The expressions of PRMT1–6, eotaxin-1, and CCR3 in lungs were screened by real-time quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT inhibitor) and small interfering RNA–PRMT1 were used to interrupt the function of PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI rats to observe the effects on inflammatory parameters. The results showed that PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI-1 and the knockdown of PRMT1 expression were able to downregulate the expressions of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells. Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary inflammation, reduce IL-4 production and humoral immune response, and abrogate eosinophil infiltration into the lungs. In summary, PRMT1 expression is upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of PRMT1 activity can abrogate IL-4–dependent eotaxin-1 production to influence the pulmonary inflammation with eosinophil infiltration. The findings may provide experimental evidence that PRMT1 plays an important role in asthma pathogenesis.

show abstract

IL-4 Induces Characteristic Th2 Responses Even in the Combined Absence of IL-5, IL-9, and IL-13

Cited by 315 publications

References 40 publications

A sticky end for gastrointestinal helminths; the role of the mucus barrier

A sticky end for gastrointestinal helminths; the role of the mucus barrier

Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Upregulated Protein Arginine Methyltransferase 1 by IL-4 Increases Eotaxin-1 Expression in Airway Epithelial Cells and Participates in Antigen-Induced Pulmonary Inflammation in Rats

Contact Info

Product

Resources

About