Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity

Pfajfer, Laurène; Mair, Nina K; Jiménez-Heredia, Raúl; Genel, Ferah; Gülez, Nesrin; Ardeniz, Ömür; Hoeger, Birgit; Bal, Sevgi Köstel; Madritsch, Christoph; Kalinichenko, Artem; Ardy, Rico Chandra; Gerçeker, Bengü; Rey-Barroso, Javier; IJspeert, Hanna; Tangye, Stuart G.; Simonitsch‐Klupp, Ingrid; Huppa, Johannes B.; Burg, Mirjam van der; Dupré, Loı̈c; Boztuğ, Kaan

doi:10.1016/j.jaci.2018.04.023

Cited by 67 publications

(89 citation statements)

References 44 publications

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“…Three reports have been published identifying children with autosomal recessive missense mutations in the WDR1 gene. WDR1 deficient patients have frequent infections, severe stomatitis, and impaired wound healing . Their neutrophils have elevated basal F‐actin levels with impaired spreading, polarization, adhesion, and chemotaxis .…”

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

“…WDR1 deficient neutrophils also have augmentation of their oxidative burst . Monocytes are similarly affected in these patients and have abnormal morphology and reduced adhesion to substrates …”

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

“…These patients have B cell lymphopenia with decreased progenitor B cells in the bone marrow and switched memory B cells in the periphery. Their percentage of Tfh cells is also decreased …”

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

“…WDR1 deficient patients have frequent infections, severe stomatitis, and impaired wound healing. [203][204][205] Their neutrophils have elevated basal F-actin levels with impaired spreading, polarization, adhesion, and chemotaxis. 203,204 WDR1 deficient neutrophils also have augmentation of their oxidative burst.…”

Section: Wdr1mentioning

confidence: 99%

“…[203][204][205] Their neutrophils have elevated basal F-actin levels with impaired spreading, polarization, adhesion, and chemotaxis. 203,204 WDR1 deficient neutrophils also have augmentation of their oxidative burst. 203 Monocytes are similarly affected in these patients and have abnormal morphology and reduced adhesion to substrates.…”

Section: Wdr1mentioning

confidence: 99%

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Primary immunodeficiencies caused by mutations in actin regulatory proteins

Janssen

2018

Immunological Reviews

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Summary The identification of patients with monogenic gene defects have illuminated the function of different proteins in the immune system, including proteins that regulate the actin cytoskeleton. Many of these actin regulatory proteins are exclusively expressed in leukocytes and regulate the formation and branching of actin filaments. Their absence or abnormal function leads to defects in immune cell shape, cellular projections, migration, and signaling. Through the study of patients’ mutations and generation of mouse models that recapitulate the patients’ phenotypes, our laboratory and others have gained a better understanding of the role these proteins play in cell biology and the underlying pathogenesis of immunodeficiencies and immune dysregulatory syndromes.

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Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

“…These patients have B cell lymphopenia with decreased progenitor B cells in the bone marrow and switched memory B cells in the periphery. Their percentage of Tfh cells is also decreased …”

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

Section: Wdr1mentioning

confidence: 99%

Section: Wdr1mentioning

confidence: 99%

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Primary immunodeficiencies caused by mutations in actin regulatory proteins

Janssen

2018

Immunological Reviews

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Autoinflammatory Diseases Presenting in the Skin

Lipsker,

Grattan,

Lovell

2024

Rook's Textbook of Dermatology

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Autoinflammatory diseases comprise a heterogeneous group of inherited monogenic and acquired polygenic multisystem disorders that may present in the skin and are therefore of importance to dermatologists. The inherited monogenic disorders typically present in childhood. Those that present with urticarial rashes are particularly important to differentiate from chronic urticaria since the pathogenesis, prognosis and treatment are completely different. Cryopyrin‐associated periodic syndrome should be suspected in children with a family history of chronic urticaria that does not respond to H 1 antihistamines and who have systemic symptoms of malaise and fever with persistently raised inflammatory indices. Autoinflammatory syndromes also may present with: unexplained fever, erysipelas‐like rash (familial Mediterranean fever), oedema (tumour necrosis factor receptor‐associated periodic syndrome), granulomatous dermatitis (Blau syndrome), an aseptic pustular dermatosis (deficiency of interleukin 1 receptor antagonist) or pyoderma gangrenosum (pyogenic sterile arthritis, acne and pyoderma gangrenosum), chilblain or acral erythematous atrophic or necrotic lesions in a toddler with neurological (Aicardi‐Goutières syndrome) or interstitial pneumonia (STING‐associated vasculopathy of infancy), lipoatrophy (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), livedo, nodules (vasculitis) and stroke (deficiency of adenosine deaminase 2), aphtous stomatis with early‐onset bowel disease (haploinsufficiency of A20 or of RELA). Acquired autoinflammatory syndromes which present in adult life include Schnitzler syndrome and adult Still disease; the differential diagnosis includes urticarial vasculitis.

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Cellular models in autoinflammatory disease research

Şen,

Balcı‐Peynircioğlu

2024

Clin & Trans Imm

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Systemic autoinflammatory diseases are a heterogeneous group of rare genetic disorders caused by dysregulation of the innate immune system. Understanding the complex mechanisms underlying these conditions is critical for developing effective treatments. Cellular models are essential for identifying new conditions and studying their pathogenesis. Traditionally, these studies have used primary cells and cell lines of disease‐relevant cell types, although newer induced pluripotent stem cell (iPSC)‐based models might have unique advantages. In this review, we discuss the three cellular models used in autoinflammatory disease research, their strengths and weaknesses, and their applications to inform future research in the field.

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Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity

Abstract: Our study identifies a novel role for WDR1 in adaptive immunity, highlighting WDR1 as a central regulator of actin turnover during formation of the B-cell and T-cell immunologic synapses.

Cited by 67 publications

References 44 publications

Primary immunodeficiencies caused by mutations in actin regulatory proteins

Primary immunodeficiencies caused by mutations in actin regulatory proteins

Autoinflammatory Diseases Presenting in the Skin

Cellular models in autoinflammatory disease research

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