A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

Hernandez, Joseph D.; Hsieh, Elena W.Y.

doi:10.1097/mop.0000000000001181

Cited by 3 publications

(1 citation statement)

References 82 publications

(244 reference statements)

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“…Human T−B+ SCID is caused by a variety of genetic lesions, with a number of such mutations impacting cytokine signaling via interleukin-2 (IL-2) family members [ 67 ], some of which have been successfully modelled in zebrafish. For instance, LOF mutations in the zebrafish il2rga gene, which encodes the IL-2 receptor γ (IL-2Rγ) common chain, resulted in severely reduced numbers of embryonic T cells, impaired juvenile TCR rearrangement and significantly reduced adult T cells and NK cells; however, B cells and myeloid cells were not affected [ 26 , 35 , 68 ].…”

Section: Zebrafish Models Of Lymphoid Disordersmentioning

confidence: 99%

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Basheer

Sertori

Liongue

et al. 2023

IJMS

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Primary immunodeficiency (PID) disorders, also commonly referred to as inborn errors of immunity, are a heterogenous group of human genetic diseases characterized by defects in immune cell development and/or function. Since these disorders are generally uncommon and occur on a variable background profile of potential genetic and environmental modifiers, animal models are critical to provide mechanistic insights as well as to create platforms to underpin therapeutic development. This review aims to review the relevance of zebrafish as an alternative genetic model for PIDs. It provides an overview of the conservation of the zebrafish immune system and details specific examples of zebrafish models for a multitude of specific human PIDs across a range of distinct categories, including severe combined immunodeficiency (SCID), combined immunodeficiency (CID), multi-system immunodeficiency, autoinflammatory disorders, neutropenia and defects in leucocyte mobility and respiratory burst. It also describes some of the diverse applications of these models, particularly in the fields of microbiology, immunology, regenerative biology and oncology.

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Section: Zebrafish Models Of Lymphoid Disordersmentioning

confidence: 99%

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Basheer

Sertori

Liongue

et al. 2023

IJMS

View full text Add to dashboard Cite

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Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology

Sommer,

Jacob,

Bargmann

et al. 2024

Clinical Immunology

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Too much of a good thing: a review of primary immune regulatory disorders

Tsilifis,

Slatter,

Gennery

2023

Front. Immunol.

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Primary immune regulatory disorders (PIRDs) are inborn errors of immunity caused by a loss in the regulatory mechanism of the inflammatory or immune response, leading to impaired immunological tolerance or an exuberant inflammatory response to various stimuli due to loss or gain of function mutations. Whilst PIRDs may feature susceptibility to recurrent, severe, or opportunistic infection in their phenotype, this group of syndromes has broadened the spectrum of disease caused by defects in immunity-related genes to include autoimmunity, autoinflammation, lymphoproliferation, malignancy, and allergy; increasing focus on PIRDs has thus redefined the classical ‘primary immunodeficiency’ as one aspect of an overarching group of inborn errors of immunity. The growing number of genetic defects associated with PIRDs has expanded our understanding of immune tolerance mechanisms and prompted identification of molecular targets for therapy. However, PIRDs remain difficult to recognize due to incomplete penetrance of their diverse phenotype, which may cross organ systems and present to multiple clinical specialists prior to review by an immunologist. Control of immune dysregulation with immunosuppressive therapies must be balanced against the enhanced infective risk posed by the underlying defect and accumulated end-organ damage, posing a challenge to clinicians. Whilst allogeneic hematopoietic stem cell transplantation may correct the underlying immune defect, identification of appropriate patients and timing of transplant is difficult. The relatively recent description of many PIRDs and rarity of individual genetic entities that comprise this group means data on natural history, clinical progression, and treatment are limited, and so international collaboration will be needed to better delineate phenotypes and the impact of existing and potential therapies. This review explores pathophysiology, clinical features, current therapeutic strategies for PIRDs including cellular platforms, and future directions for research.

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A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

Cited by 3 publications

References 82 publications

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology

Too much of a good thing: a review of primary immune regulatory disorders

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