Therapeutic activity of an interleukin‐4/interleukin‐13 dual antagonist on oxazolone‐induced colitis in mice

Kasaian, Marion T.; Page, Karen; Fish, Susan; Brennan, Agnes; Cook, Timothy A.; Moreira, Karen Betancourt; Zhang, Melvin; Jesson, Michael I.; Marquette, Kimberly; Agostinelli, Rita; Lee, Julie; Williams, Cara; Tchistiakova, Lioudmila; Thakker, Paresh

doi:10.1111/imm.12319

Cited by 44 publications

(39 citation statements)

References 53 publications

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“…Thorough elucidation of these groups of markers, or panels, has revealed that these phenotypes are distinguished by expression differences in chemokines, chemokine receptors, enzymes, costimulatory molecules, Toll receptors, cytokines, and cytokine receptors. [39][40][41][42][43] M1 macrophages express inducible nitric oxide synthase (iNOS), the primary marker that confirms the response of these cells in a specific disease (Table 1). [44][45][46] However, a surface marker that defines the identity of M1 macrophages has not yet been identified.…”

Section: Macrophage Phenotypesmentioning

confidence: 92%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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Section: Macrophage Phenotypesmentioning

confidence: 92%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

View full text Add to dashboard Cite

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“…As with the failure of anti-IFNγ in CD, this result seems to suggest that blocking a single Th2 cytokine is not sufficient to induce a therapeutic response. Anti-IL-4/13 bi-specific antibodies 81 are in development for asthma, and show therapeutic effects in Th2-associated colitis 82 . Thus, it will be of interest to determine if this approach, or perhaps other combinatorial approaches (for example also targeting IL-5 and/or GM-CSF), may be more broadly therapeutic in UC.…”

Section: Cd4+ T Cells In Ibdmentioning

confidence: 99%

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Chen

Sundrud

2016

Inflammatory Bowel Diseases

129

104

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Pathogenesis of the inflammatory bowel diseases (IBDs) ulcerative colitis (UC) and Crohn’s disease (CD) involve pro-inflammatory changes within the microbiota, chronic immune-mediated inflammatory responses, and epithelial dysfunction. Converging data from genome-wide association studies (GWAS), mouse models of IBD, and clinical trials indicate that cytokines are key effectors of both normal homeostasis and chronic inflammation in the gut. Yet still many questions remain concerning the role of specific cytokines in different IBDs, within distinct regions of the gut, and with regard cellular mechanisms of action. Here we review current and emerging concepts concerning the role of cytokines in IBD, with a focus on immune regulation, T cell subsets, and potential clinical applications.

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“…Recently, a novel treatment was tested in oxazolone treated mice, utilizing a bifunctional IL-4/IL-13 antagonist, in the hopes that such combinatorial blockade would overcome the redundant effects of these cytokines (29). Binding of IL-13 was accomplished via a derivative of the murine IL-13Ra2 extracellular sequence and of IL-4 via a derivative of rat anti-mouse IL-4 mAb 11B11.…”

Section: Downstream Effectors Of Th2 Immunitymentioning

confidence: 99%

Role of type 2 immunity in intestinal inflammation

Bamias

Cominelli

2015

Current Opinion in Gastroenterology

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Purpose of Review Type 2 (Th2) immune responses play important roles in intestinal immunity by contributing to the maintenance of mucosal homeostasis, conferring protection against helminthic inflection, but also participating in pro-inflammatory pathways in chronic intestinal inflammatory disorders, including inflammatory bowel disease (IBD). The current review focuses on recent developments regarding the role of type 2 responses in intestinal inflammation. Recent Findings Th2 gut mucosal responses are promoted by mediators that are released following injury to the epithelium and act as alarmin-type danger signals. IL-33 is prominent among such factors and demonstrates a dichotomous function exerting either protective or pro-inflammatory effects, depending on its cellular compartmentalization. The pool of type 2 effector cells has been enriched recently to include not only classical CD4+ Th2 lymphocytes but also a subset of innate lymphocytes (ILC2) that express the transcriptional factor GATA3 and secrete IL-4, IL-5, and IL-13. ILC2 play important roles during infection with helminthes and bi-directionally interact with Th2 CD4+ lymphocytes, thus, establishing a transition from innate to adaptive immunological pathways. Type 2 responses are also involved in pro-inflammatory pathways at the intestinal mucosa and neutralization of the pivotal cytokines IL-4 and IL-13 has been shown to regulate experimental intestinal inflammation. In striking contrast, however, neutralization of human IL-13 had no therapeutic effect in patients with ulcerative colitis. Summary Further studies will be required to delineate the specific mechanisms of type 2 mucosal immunity in IBD and examine the applicability of Th2-targeted therapies for intestinal inflammation.

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Therapeutic activity of an interleukin‐4/interleukin‐13 dual antagonist on oxazolone‐induced colitis in mice

Cited by 44 publications

References 53 publications

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Role of type 2 immunity in intestinal inflammation

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