Dual T cell– and B cell–intrinsic deficiency in humans with biallelic <i>RLTPR</i> mutations

Wang, Yi; Cindy, S.; Ling, Yun; Bousfiha, Aziz; Camcioğlu, Yıldız; Jacquot, Serge; Payne, Kathryn; Crestani, Elena; Roncagalli, Romain; Belkadi, Aziz; Kerner, Gaspard; Lorenzo, Lazaro; Deswarte, Caroline; Chrabieh, Maya; Patin, Étienne; Vincent, Quentin B.; Müller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Ailal, Fatima; Quintana-Murci, Lluı́s; Fraïtag, Sylvie; Alyanakian, Marie‐Alexandra; Leruez‐Ville, Marianne; Pïcard, Capucine; Puel, Anne; Bustamante, Jacinta; Boisson–Dupuis, Stéphanie; Malissen, Marie; Malissen, Bernard; Abel, Laurent; Hovnanian, Alain; Notarangelo, Luigi D.; Jouanguy, Emmanuelle; Tangye, Stuart G.; Béziat, Vivien; Casanova, Jean‐Laurent

doi:10.1084/jem.20160576

Cited by 102 publications

(147 citation statements)

References 91 publications

(132 reference statements)

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“…Patients lacked regulatory T-cells and suffered from immunodeficiency syndromes similar to those in patients in the studies discussed earlier (Sorte et al , 2016; Wang et al , 2016; Schober et al , 2017). In T-cells isolated from patients, levels of F-actin at the leading edge were decreased and the microtubule network was disorganized.…”

Section: Roles Of Carmils At the Cellular And Organismal Levelsmentioning

confidence: 74%

CARMIL family proteins as multidomain regulators of actin-based motility

Stark

Lanier

Cooper

2017

MBoC

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CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity. Vertebrates have three highly conserved genes and expressed isoforms of CARMIL with distinct and overlapping localizations and functions in cells. Various domains of these CARMIL isoforms interact with plasma membranes, vimentin intermediate filaments, SH3-containing class I myosins, the dual-GEF Trio, and other adaptors and signaling molecules. These biochemical properties suggest that CARMILs play a variety of membrane-associated functions related to actin assembly and signaling. CARMIL mutations and variants have been implicated in several human diseases. We focus on roles for CARMILs in signaling in addition to their function as regulators of CP and actin.

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Section: Roles Of Carmils At the Cellular And Organismal Levelsmentioning

confidence: 74%

CARMIL family proteins as multidomain regulators of actin-based motility

Stark

Lanier

Cooper

2017

MBoC

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“…Likewise, listed in the black portion are non-HLA genes with alleles that associate with Mycobacteria disease susceptibility 160–162,299–315 . Listed in the gray overlap are nine genes with alleles that associate with both Candida and Mycobacteria disease susceptibility: IRF8 154 , MBL2 156,316,317 , TLR2 157,314,318 , IL10 319–321 , IL12B 110,320 , IL12RB1 322–325 , RLTPR 326 , RORC 327 and STAT1 206,207,328–332 . As indicated by labels on the left, each gene is further classified as being a regulator of either pathogen recognition (top row), cytokine responsiveness (middle row) or antimicrobial effector mechanisms (bottom row).…”

Section: Figurementioning

confidence: 99%

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Robinson

Huppler

2017

Cytokine

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Mycobacteria and Candida species include significant human pathogens that can cause localized or disseminated infections. Although these organisms may appear to have little in common, several shared pathways of immune recognition and response are important for both control and infection-related pathology. In this article, we compare and contrast the innate and adaptive components of the immune system that pertain to these infections in humans and animal models. We also explore a relatively new concept in the mycobacterial field: biological commensalism. Similar to the well-established model of Candida infection, Mycobacterial species colonize their human hosts in equilibrium with the immune response. Perturbations in the immune response permit the progression to pathologic disease at the expense of the host. Understanding the immune factors required to maintain commensalism may aid with the development of diagnostic and treatment strategies for both categories of pathogens.

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“…When CD28 signalling is blocked at the time of T‐cell priming, T‐cell activation is suppressed and this prevents Tfh cell differentiation in vivo . CD28 co‐stimulation depends upon the RLTPR, a scaffold protein that links CD28 to the CARD11/CARMA1 cytosolic adapter and to the nuclear factor‐ κ B (NF‐ κ B) pathway . Mice and humans deficient in RLTPR have very few Tfh cells and this is associated with defects in activation‐induced expression of CD40L, ICOS and RelA phosphorylation (indicative of impaired NF‐ κ B signalling) .…”

Section: The Importance Of Co‐receptor Signals In Tfh Cell Differentimentioning

confidence: 99%

Signals that drive T follicular helper cell formation

Webb

Linterman

2017

Immunology

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SummaryT follicular helper (Tfh) cells are a distinct type of CD4 + T cell specialized in providing help to B cells during the germinal centre (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of Tfh cells can result in autoimmunity whereas too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate but limited help to B cells. Unlike the majority of other CD4 + T-cell subsets, Tfh cell differentiation occurs in three phases defined by their anatomical location. During each phase of differentiation the emerging Tfh cells express distinct patterns of coreceptors, which work together with the T-cell receptor (TCR) to drive Tfh differentiation. These signals provided by both TCR and co-receptors during Tfh differentiation alter proliferation, survival, metabolism, cytokine production and transcription factor expression. This review will discuss how engagement of TCR and co-receptors work together to shape the formation and function of Tfh cells.

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Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations

Cited by 102 publications

References 91 publications

CARMIL family proteins as multidomain regulators of actin-based motility

CARMIL family proteins as multidomain regulators of actin-based motility

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Signals that drive T follicular helper cell formation

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