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1.
Nat Immunol ; 25(7): 1193-1206, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38834865

RESUMEN

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA2, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKß-NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.


Asunto(s)
Movimiento Celular , Células Dendríticas , Homeostasis , Ganglios Linfáticos , Ratones Endogámicos C57BL , Receptores CCR7 , Animales , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/citología , Receptores CCR7/metabolismo , Ratones , Movimiento Celular/inmunología , Forma de la Célula , FN-kappa B/metabolismo , Ratones Noqueados , Transducción de Señal/inmunología , Quinasa I-kappa B/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo
2.
Cell ; 183(2): 411-428.e16, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32970988

RESUMEN

The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must therefore tightly regulate fluid influx to control absorption of fungal metabolites, which can be toxic to epithelial cells and lead to barrier dysfunction. How this is achieved remains unknown. Here, we describe a mechanism by which the innate immune system allows rapid quality check of absorbed fluids to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages that are equipped with "balloon-like" protrusions (BLPs) inserted in the epithelium, which sample absorbed fluids. In the absence of macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to their death and subsequent loss of epithelial barrier integrity. These results reveal an unexpected and essential role of macrophages in the maintenance of colon-microbiota interactions in homeostasis. VIDEO ABSTRACT.


Asunto(s)
Microbioma Gastrointestinal/fisiología , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Animales , Colon/metabolismo , Células Epiteliales/metabolismo , Epitelio , Femenino , Homeostasis , Inmunidad Innata/inmunología , Mucosa Intestinal/microbiología , Macrófagos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota , Transducción de Señal
3.
Immunity ; 55(6): 965-967, 2022 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-35704996

RESUMEN

The relevance of cross-dressing as an antigen presentation mechanism in antitumor responses is not fully understood. In this issue of Immunity, MacNabb et al. (2022) report that dendritic cells use cross-dressing as an effective mechanism to trigger CD8+ T cell antitumor immunity.


Asunto(s)
Presentación de Antígeno , Células Dendríticas , Linfocitos T CD8-positivos , Reactividad Cruzada
4.
Immunity ; 55(1): 129-144.e8, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34910930

RESUMEN

Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show that the small intestine included two pools of cDC2s originating from common pre-DC precursors: (1) lamina propria (LP) CD103+CD11b+ cDC2s that were mature-like proinflammatory cells and (2) intraepithelial cDC2s that exhibited an immature-like phenotype as well as tolerogenic properties. These phenotypes resulted from the action of food-derived retinoic acid (ATRA), which enhanced actomyosin contractility and promoted LP cDC2 transmigration into the epithelium. There, cDC2s were imprinted by environmental cues, including ATRA itself and the mucus component Muc2. Hence, by reaching distinct subtissular niches, DCs can exist as immature and mature cells within the same tissue, revealing an additional mechanism of DC functional diversification.


Asunto(s)
Células Dendríticas/inmunología , Inflamación/inmunología , Mucosa Intestinal/patología , Linfocitos T/inmunología , Actomiosina/metabolismo , Animales , Presentación de Antígeno , Antígenos CD/metabolismo , Antígeno CD11b/metabolismo , Diferenciación Celular , Movimiento Celular , Células Cultivadas , Tolerancia Inmunológica , Cadenas alfa de Integrinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mucina 2/inmunología , Tretinoina/metabolismo
5.
Immunity ; 55(12): 2336-2351.e12, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36462502

RESUMEN

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue remodeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for organoid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.


Asunto(s)
Colitis , Mucosa Intestinal , Animales , Cicatrización de Heridas , Células Epiteliales/metabolismo , Epitelio , Modelos Animales de Enfermedad
6.
Cell ; 161(2): 374-86, 2015 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-25799384

RESUMEN

Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.


Asunto(s)
Actinas/metabolismo , Movimiento Celular , Modelos Biológicos , Animales , Línea Celular , Polaridad Celular , Células Cultivadas , Citoesqueleto/metabolismo , Humanos , Ratones Endogámicos C57BL , Oryzias
7.
Semin Cell Dev Biol ; 150-151: 50-57, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36635104

RESUMEN

The intestine comprises the largest proportion of immune cells in the body. It is continuously exposed to new antigens and immune stimuli from the diet, microbiota but also from intestinal pathogens. In this review, we describe the main populations of immune cells present along the intestine, both from the innate and adaptive immune system. We later discuss how intestinal niches significantly impact the phenotype and function of gut immune populations at steady state and upon infection.


Asunto(s)
Inmunidad Mucosa , Mucosa Intestinal , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Inmunidad Innata , Inmunidad Adaptativa
8.
Immunity ; 45(6): 1205-1218, 2016 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-28002729

RESUMEN

Inflammation triggers the differentiation of Ly6Chi monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3+CD11c-MHCII+PU.1hi subset. This subset acted as a precursor for FcγRIII+PD-L2+CD209a+, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3-CD11c-MHCII-PU.1lo monocytes differentiated into FcγRIII+PD-L2-CD209a-iNOS+ macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1+/- mice had reduced Flt3+CD11c-MHCII+ monocytes and GM-CSF-dependent FcγRIII+PD-L2+CD209a+ moDCs but generated iNOS+ macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS+ macrophages or moDCs.


Asunto(s)
Diferenciación Celular/inmunología , Células Dendríticas/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Traslado Adoptivo , Animales , Antígenos Ly/inmunología , Separación Celular , Células Dendríticas/citología , Citometría de Flujo , Macrófagos/citología , Ratones , Monocitos/citología , Óxido Nítrico Sintasa de Tipo II/inmunología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa
9.
Immunity ; 43(6): 1087-100, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26682983

RESUMEN

The initiation of cytotoxic immune responses by dendritic cells (DCs) requires the presentation of antigenic peptides derived from phagocytosed microbes and infected or dead cells to CD8(+) T cells, a process called cross-presentation. Antigen cross-presentation by non-activated DCs, however, is not sufficient for the effective induction of immune responses. Additionally, DCs need to be activated through innate receptors, like Toll-like receptors (TLRs). During DC maturation, cross-presentation efficiency is first upregulated and then turned off. Here we show that during this transient phase of enhanced cross-presentation, phago-lysosome fusion was blocked by the topological re-organization of lysosomes into perinuclear clusters. LPS-induced lysosomal clustering, inhibition of phago-lysosome fusion and enhanced cross-presentation, all required expression of the GTPase Rab34. We conclude that TLR4 engagement induces a Rab34-dependent re-organization of lysosomal distribution that delays antigen degradation to transiently enhance cross-presentation, thereby optimizing the priming of CD8(+) T cell responses against pathogens.


Asunto(s)
Presentación de Antígeno/inmunología , Reactividad Cruzada/inmunología , Células Dendríticas/inmunología , Receptor Toll-Like 4/inmunología , Animales , Antígenos/inmunología , Linfocitos T CD8-positivos/inmunología , Citotoxicidad Inmunológica/inmunología , Femenino , Citometría de Flujo , Lisosomas/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fagosomas/inmunología , ARN Interferente Pequeño , Transfección , Proteínas de Unión al GTP rab/inmunología
10.
Proc Natl Acad Sci U S A ; 118(18)2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33903241

RESUMEN

Sprouting angiogenesis is fundamental for development and contributes to cancer, diabetic retinopathy, and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on how tip cells invade into tissues. Here, we show that endothelial tip cells use dactylopodia as the main cellular protrusion for invasion into nonvascular extracellular matrix. We show that dactylopodia and filopodia protrusions are balanced by myosin IIA (NMIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of NMIIA promotes excessive dactylopodia formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents dactylopodia development and leads to excessive filopodia formation. We further show that NMIIA inhibits Rac1-dependent activation of Arp2/3 by regulating the maturation state of focal adhesions. Our discoveries establish a comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way toward strategies to block invasive tip cells during sprouting angiogenesis.


Asunto(s)
Células Endoteliales/citología , Miosina Tipo IIA no Muscular/genética , Seudópodos/genética , Proteína de Unión al GTP rac1/genética , Complejo 2-3 Proteico Relacionado con la Actina/química , Complejo 2-3 Proteico Relacionado con la Actina/genética , Animales , Extensiones de la Superficie Celular , Células Endoteliales/metabolismo , Ratones , Neovascularización Patológica/genética , Neovascularización Fisiológica/genética , Miosina Tipo IIA no Muscular/química , Activación Transcripcional/genética
11.
EMBO J ; 38(11)2019 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-30902847

RESUMEN

The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here, we show that increasing densities of actin filaments at the centrosome of lymphocytes are correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in disassembly of centrosomal actin and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed in vitro reconstitution assays based on (i) purified centrosomes and (ii) on the co-micropatterning of microtubule seeds and actin filaments. These two assays demonstrated that actin filaments constitute a physical barrier blocking elongation of nascent microtubules. Finally, we showed that cell adhesion and cell spreading lead to lower densities of centrosomal actin, thus resulting in higher microtubule growth. We therefore propose a novel mechanism, by which the number of centrosomal microtubules is regulated by cell adhesion and actin-network architecture.


Asunto(s)
Citoesqueleto de Actina/fisiología , Centrosoma/metabolismo , Microtúbulos/metabolismo , Actinas/metabolismo , Animales , Bovinos , Células Cultivadas , Humanos , Células Jurkat , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo
12.
J Cell Sci ; 134(18)2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34494097

RESUMEN

Lysosomal signaling facilitates the migration of immune cells by releasing Ca2+ to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the trans-Golgi network (TGN). Here, we show that Rab7b regulates the migration of dendritic cells (DCs) in one- and three-dimensional environments. DCs are immune sentinels that transport antigens from peripheral tissues to lymph nodes to activate T lymphocytes and initiate adaptive immune responses. We found that the lack of Rab7b reduces myosin II light chain phosphorylation and the activation of the transcription factor EB (TFEB), which controls lysosomal signaling and is required for fast DC migration. Furthermore, we demonstrate that Rab7b interacts with the lysosomal Ca2+ channel TRPML1 (also known as MCOLN1), enabling the local activation of myosin II at the cell rear. Taken together, our findings identify Rab7b as the missing physical link between lysosomes and the actomyosin cytoskeleton, allowing control of immune cell migration through lysosomal signaling. This article has an associated First Person interview with the first author of the paper.


Asunto(s)
Actomiosina , Lisosomas , Citoesqueleto , Células Dendríticas , Endosomas , Humanos
13.
Subcell Biochem ; 98: 85-102, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35378704

RESUMEN

Macropinocytosis is a nonspecific mechanism by which cells compulsively "drink" the surrounding extracellular fluids in order to feed themselves or sample the molecules therein, hence gaining information about their environment. This process is cell-intrinsically incompatible with the migration of many cells, implying that the two functions are antagonistic. The migrating cell uses a molecular switch to stop and explore its surrounding fluid by macropinocytosis, after which it employs the same molecular machinery to start migrating again to examine another location. This cycle of migration/macropinocytosis allows cells to explore tissues, and it is key to a range of physiological processes. Evidence of this evolutionarily conserved antagonism between the two processes can be found in several cell types-immune cells, for example, being particularly adept-and ancient organisms (e.g., the social amoeba Dictyostelium discoideum). How macropinocytosis and migration are negatively coupled is the subject of this chapter.


Asunto(s)
Dictyostelium , Movimiento Celular , Dictyostelium/metabolismo , Pinocitosis/fisiología
14.
Proc Natl Acad Sci U S A ; 117(2): 826-835, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31882452

RESUMEN

Dendritic cells "patrol" the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.


Asunto(s)
Actinas/metabolismo , Movimiento Celular/fisiología , Polaridad Celular/fisiología , Señales (Psicología) , Células Dendríticas/fisiología , Actinas/ultraestructura , Médula Ósea , Membrana Celular , Forma de la Célula , Colágeno , Células Dendríticas/citología , Geles , Humanos , Polimerizacion
15.
J Cell Sci ; 133(5)2020 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-32122988

RESUMEN

Studies in recent years have shed light on the particular features of cytoskeleton dynamics in immune cells, challenging the classical picture drawn from typical adherent cell lines. New mechanisms linking the dynamics of the membrane-cytoskeleton interface to the mechanical properties of immune cells have been uncovered and shown to be essential for immune surveillance functions. In this Essay, we discuss these features, and propose immune cells as a new playground for cell biologists who try to understand how cells adapt to different microenvironments to fulfil their functions efficiently.


Asunto(s)
Citoesqueleto
16.
Nat Immunol ; 11(10): 953-61, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20835229

RESUMEN

During trafficking through tissues, T cells fine-tune their motility to balance the extent and duration of cell-surface contacts versus the need to traverse an entire organ. Here we show that in vivo, myosin IIA-deficient T cells had a triad of defects, including overadherence to high-endothelial venules, less interstitial migration and inefficient completion of recirculation through lymph nodes. Spatiotemporal analysis of three-dimensional motility in microchannels showed that the degree of confinement and myosin IIA function, rather than integrin adhesion (as proposed by the haptokinetic model), optimized motility rate. This motility occurred via a myosin IIA-dependent rapid 'walking' mode with multiple small and simultaneous adhesions to the substrate, which prevented spurious and prolonged adhesions. Adhesion discrimination provided by myosin IIA is thus necessary for the optimization of motility through complex tissues.


Asunto(s)
Adhesión Celular/fisiología , Movimiento Celular , Ganglios Linfáticos/inmunología , Miosina Tipo IIA no Muscular/fisiología , Linfocitos T/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
17.
Trends Immunol ; 39(8): 632-643, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29779848

RESUMEN

The function of most immune cells depends on their ability to migrate through complex microenvironments, either randomly to patrol for the presence of antigens or directionally to reach their next site of action. The actin cytoskeleton and its partners are key conductors of immune cell migration as they control the intrinsic migratory properties of leukocytes as well as their capacity to respond to cues present in their environment. In this review we focus on the latest discoveries regarding the role of the actomyosin cytoskeleton in optimizing immune cell migration in complex environments, with a special focus on recent insights provided by physical modeling.


Asunto(s)
Citoesqueleto de Actina/fisiología , Actomiosina/metabolismo , Movimiento Celular , Microambiente Celular , Leucocitos/fisiología , Animales , Humanos
18.
Immunity ; 37(2): 351-63, 2012 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-22683126

RESUMEN

Upon antigen recognition, T cells form either static (synapses) or migratory (kinapses) contacts with antigen-presenting cells. Addressing whether synapses and kinapses result in distinct T cell receptor (TCR) signals has been hampered by the inability to simultaneously assess T cell phenotype and behavior. Here, we introduced dynamic in situ cytometry (DISC), a combination of intravital multiphoton imaging and flow cytometry-like phenotypic analysis. Taking advantage of CD62L shedding as a marker of early TCR signaling, we examined how T cells sense TCR ligands of varying affinities in vivo. We uncovered three modes of antigen recognition: synapses with the strongest TCR signals, kinapses with robust signaling, and kinapses with weak signaling. As illustrated here, the DISC approach should provide unique opportunities to link immune cell behavior to phenotype and function in vivo.


Asunto(s)
Citometría de Flujo/métodos , Sinapsis Inmunológicas/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal/inmunología , Linfocitos T/inmunología , Animales , Presentación de Antígeno/inmunología , Movimiento Celular/inmunología , Rastreo Celular , Antígenos H-2/inmunología , Antígenos H-2/metabolismo , Sinapsis Inmunológicas/metabolismo , Selectina L/inmunología , Selectina L/metabolismo , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/citología , Linfocitos T/metabolismo
19.
Immunity ; 35(3): 361-74, 2011 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-21820334

RESUMEN

Engagement of the B cell receptor (BCR) by surface-tethered antigens (Ag) leads to formation of a synapse that promotes Ag uptake for presentation onto major histocompatibility complex class II (MHCII) molecules. We have highlighted the membrane trafficking events and associated molecular mechanisms involved in Ag extraction and processing at the B cell synapse. MHCII-containing lysosomes are recruited to the synapse where they locally undergo exocytosis, allowing synapse acidification and the extracellular release of hydrolases that promote the extraction of the immobilized Ag. Lysosome recruitment and secretion results from the polarization of the microtubule-organizing center (MTOC), which relies on the cell division cycle (Cdc42)-downstream effector, atypical protein kinase C (aPKCζ). aPKCζ is phosphorylated upon BCR engagement, associates to lysosomal vesicles, and is required for their polarized secretion at the B cell synapse. Regulation of B lymphocyte polarity therefore emerges as a central mechanism that couples Ag extraction to Ag processing and presentation.


Asunto(s)
Presentación de Antígeno , Linfocitos B/inmunología , Sinapsis Inmunológicas , Lisosomas , Receptores de Antígenos de Linfocitos B/fisiología , Animales , Polaridad Celular , Lisosomas/metabolismo , Ratones , Proteína Quinasa C/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Proteína de Unión al GTP cdc42/inmunología
20.
Immunol Rev ; 272(1): 39-51, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27319341

RESUMEN

Antigen presentation refers to the ability of cells to show MHC-associated determinants to T lymphocytes, leading to their activation. MHC class II molecules mainly present peptide-derived antigens that are internalized by endocytosis in antigen-presenting cells (APCs). Here, we describe how the interface between cellular membranes and the cytoskeleton regulates the various steps that lead to the presentation of exogenous antigens on MHC class II molecules in the two main types of APCs: dendritic cells (DCs) and B lymphocytes. This includes antigen uptake, processing, APC migration, and APC-T cell interactions. We further discuss how the interaction between APC-specific molecules and cytoskeleton elements allows the coordination of antigen presentation and cell migration in time and space.


Asunto(s)
Presentación de Antígeno , Linfocitos B/inmunología , Membrana Celular/metabolismo , Citoesqueleto/metabolismo , Células Dendríticas/inmunología , Linfocitos T/inmunología , Animales , Antígenos/metabolismo , Movimiento Celular , Endocitosis , Antígenos de Histocompatibilidad/metabolismo , Humanos , Sinapsis Inmunológicas , Activación de Linfocitos , Péptidos/metabolismo
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