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1.
Front Immunol ; 15: 1285215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38629063

RESUMEN

The analytical capability of flow cytometry is crucial for differentiating the growing number of cell subsets found in human blood. This is important for accurate immunophenotyping of patients with few cells and a large number of parameters to monitor. Here, we present a 43-parameter panel to analyze peripheral blood mononuclear cells from healthy individuals using 41 fluorescence-labelled monoclonal antibodies, an autofluorescent channel, and a viability dye. We demonstrate minimal population distortions that lead to optimized population identification and reproducible results. We have applied an advanced approach in panel design, in selection of sample acquisition parameters and in data analysis. Appropriate autofluorescence identification and integration in the unmixing matrix, allowed for resolution of unspecific signals and increased dimensionality. Addition of one laser without assigned fluorochrome resulted in decreased fluorescence spill over and improved discrimination of cell subsets. It also increased the staining index when autofluorescence was integrated in the matrix. We conclude that spectral flow cytometry is a highly valuable tool for high-end immunophenotyping, and that fine-tuning of major experimental steps is key for taking advantage of its full capacity.


Asunto(s)
Colorantes Fluorescentes , Leucocitos Mononucleares , Humanos , Anticuerpos Monoclonales , Recuento de Leucocitos , Luz
2.
STAR Protoc ; 4(4): 102734, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38032799

RESUMEN

Here, we present a protocol for setting three spectral flow cytometry panels for the characterization of human unconventional CD8+NKG2A/C+ T cells as well as other T and natural killer cell subsets. We describe steps for standardizing, preparing, and staining the cells, the experimental setup, and the final data analysis. This protocol should be advantageous in various settings including immunophenotyping of limited samples, immune function evaluation/monitoring, as well as research in oncology, autoimmune, and infectious diseases.


Asunto(s)
Células Asesinas Naturales , Linfocitos T , Humanos , Citometría de Flujo/métodos , Inmunofenotipificación , Linfocitos T CD8-positivos
3.
Front Immunol ; 14: 1163466, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37533857

RESUMEN

Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. Our recent work indicates that the APC protein is involved in various phases of both CD4 and CD8 T cells responses. This prompted us to investigate an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. We characterized the immune cell repertoire in peripheral blood and the capacity of immune cells to respond ex vivo to different stimuli either in whole blood or in purified T cells. A variety of experimental approaches were used, including, pultiparamater flow cytometry, NanosString gene expression profiling, Multiplex and regular ELISA, confocal microscopy and computer-based image analyis methods. We found that the percentage of several T and natural killer (NK) cell populations, the expression of several genes induced upon innate or adaptive immune stimulation and the production of several cytokines and chemokines was different. Moreover, the capacity of T cells to migrate in response to chemokine was consistently altered. Finally, immunological synapses between FAP cytotoxic T cells and tumor target cells were more poorly structured. Our findings of this pilot study suggest that mild but multiple immune cell dysfunctions, together with intestinal epithelial dysplasia in FAP subjects, may facilitate the long-term polyposis and colorectal tumor development. Although at an initial discovery phase due to the limited sample size of this rare disease cohort, our findings open new perspectives to consider immune cell abnormalities into polyposis pathology.


Asunto(s)
Poliposis Adenomatosa del Colon , Neoplasias Colorrectales , Linfocitos T , Humanos , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/patología , Movimiento Celular/genética , Neoplasias Colorrectales/genética , Genes APC , Mutación , Proyectos Piloto , Linfocitos T/inmunología
4.
Proc Natl Acad Sci U S A ; 120(26): e2221744120, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37339214

RESUMEN

Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. As a result, the search for curative treatments, which are sorely lacking in the hearing field, has become a potentially achievable objective, particularly via cochlear gene and cell therapies. To this end, a complete inventory of cochlear cell types, with an in-depth characterization of their gene expression profiles right up to their final differentiation, is indispensable. We therefore generated a single-cell transcriptomic atlas of the mouse cochlea based on an analysis of more than 120,000 cells on postnatal day 8 (P8), during the prehearing period, P12, corresponding to hearing onset, and P20, when cochlear maturation is almost complete. By combining whole-cell and nuclear transcript analyses with extensive in situ RNA hybridization assays, we characterized the transcriptomic signatures covering nearly all cochlear cell types and developed cell type-specific markers. Three cell types were discovered; two of them contribute to the modiolus which houses the primary auditory neurons and blood vessels, and the third one consists in cells lining the scala vestibuli. The results also shed light on the molecular basis of the tonotopic gradient of the biophysical characteristics of the basilar membrane that critically underlies cochlear passive sound frequency analysis. Finally, overlooked expression of deafness genes in several cochlear cell types was also unveiled. This atlas paves the way for the deciphering of the gene regulatory networks controlling cochlear cell differentiation and maturation, essential for the development of effective targeted treatments.


Asunto(s)
Sordera , Transcriptoma , Animales , Ratones , Cóclea/fisiología , Membrana Basilar , Audición/fisiología , Sordera/metabolismo
5.
Sci Adv ; 8(50): eadd0695, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36516250

RESUMEN

The coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we developed and applied an unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs underlying the emergence of specialized cell types during mouse limb development and their spatial integration. We identify multiple transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, suggesting two parallel yet highly interconnected regulatory systems. We demonstrate that the embryonic limb undergoes a complex multiscale reorganization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, alterations of preexisting cell states' molecular identities, and changes in their relative spatial distribution. Our study shows how multidimensional single-cell, spatially resolved molecular atlases can allow the deconvolution of spatial identity and cell fate and reveal the interconnected genetic networks that regulate organogenesis and its reorganization upon genetic alterations.

6.
Cytometry A ; 101(11): 960-969, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35491762

RESUMEN

The fetal liver (FL) is the main hematopoietic organ during embryonic development. The FL is also the unique anatomical site where hematopoietic stem cells expand before colonizing the bone marrow, where they ensure life-long blood cell production and become mostly resting. The identification of the different cell types that comprise the hematopoietic stroma in the FL is essential to understand the signals required for the expansion and differentiation of the hematopoietic stem cells. We used a panel of monoclonal antibodies to identify FL stromal cells in a 5-laser equipped spectral flow cytometry (FCM) analyzer. The "Autofluorescence Finder" of SONY ID7000 software identified two distinct autofluorescence emission spectra. Using autofluorescence as a fluorescence parameter we could assign the two autofluorescent signals to three distinct cell types and identified surface markers that characterize these populations. We found that one autofluorescent population corresponds to hepatoblast-like cells and cholangiocytes whereas the other expresses mesenchymal transcripts and was identified as stellate cells. Importantly, after birth, autofluorescence becomes the unique identifying property of hepatoblast-like cells because mature cholangiocytes are no longer autofluorescent. These results show that autofluorescence used as a parameter in spectral FCM is a useful tool to identify new cell subsets that are difficult to analyze in conventional FCM.


Asunto(s)
Células Madre Hematopoyéticas , Hígado , Embarazo , Femenino , Humanos , Células de la Médula Ósea , Diferenciación Celular , Médula Ósea , Citometría de Flujo
7.
Methods Mol Biol ; 2450: 565-581, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35359329

RESUMEN

Cnidarians have historically served as excellent laboratory models for regenerative development given their capacity to regrow large portions of the adult organism. This capacity is notably absent or poorly developed in the powerful genetic laboratory models Drosophila, C. elegans, and mouse. Increasingly, development of genetic and genomic resources and the application of next-generation sequencing-based techniques in cnidarian systems has further expanded the potential of cnidarian regenerative models. Here, we present a workflow for the characterization of the regenerative response in the sea anemone Nematostella vectensis utilizing fluorescence-activated cell sorting and a plate-based single-cell RNA-sequencing pipeline. This approach can characterize the transcriptional response during regeneration in distinct populations of cells, thus providing a quantitative view of a whole organism process at cellular resolution.


Asunto(s)
Anémonas de Mar , Animales , Caenorhabditis elegans/genética , Genómica , Ratones , Transcriptoma
8.
J Vis Exp ; (180)2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35188133

RESUMEN

The brain is no longer considered as an organ functioning in isolation; accumulating evidence suggests that changes in the peripheral immune system can indirectly shape brain function. At the interface between the brain and the systemic circulation, the choroid plexuses (CP), which constitute the blood-cerebrospinal fluid barrier, have been highlighted as a key site of periphery-to-brain communication. CP produce the cerebrospinal fluid, neurotrophic factors, and signaling molecules that can shape brain homeostasis. CP are also an active immunological niche. In contrast to the brain parenchyma, which is populated mainly by microglia under physiological conditions, the heterogeneity of CP immune cells recapitulates the diversity found in other peripheral organs. The CP immune cell diversity and activity change with aging, stress, and disease and modulate the activity of the CP epithelium, thereby indirectly shaping brain function. The goal of this protocol is to isolate murine CP and identify about 90% of the main immune subsets that populate them. This method is a tool to characterize CP immune cells and understand their function in orchestrating periphery-to-brain communication. The proposed protocol may help decipher how CP immune cells indirectly modulate brain function in health and across various disease conditions.


Asunto(s)
Barrera Hematoencefálica , Plexo Coroideo , Envejecimiento , Animales , Barrera Hematoencefálica/fisiología , Encéfalo/fisiología , Coroides , Ratones
9.
Nat Commun ; 11(1): 1941, 2020 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-32321914

RESUMEN

Cytokinesis requires the constriction of ESCRT-III filaments on the side of the midbody, where abscission occurs. After ESCRT recruitment at the midbody, it is not known how the ESCRT-III machinery localizes to the abscission site. To reveal actors involved in abscission, we obtained the proteome of intact, post-abscission midbodies (Flemmingsome) and identified 489 proteins enriched in this organelle. Among these proteins, we further characterized a plasma membrane-to-ESCRT module composed of the transmembrane proteoglycan syndecan-4, ALIX and syntenin, a protein that bridges ESCRT-III/ALIX to syndecans. The three proteins are highly recruited first at the midbody then at the abscission site, and their depletion delays abscission. Mechanistically, direct interactions between ALIX, syntenin and syndecan-4 are essential for proper enrichment of the ESCRT-III machinery at the abscission site, but not at the midbody. We propose that the ESCRT-III machinery must be physically coupled to a membrane protein at the cytokinetic abscission site for efficient scission, uncovering common requirements in cytokinesis, exosome formation and HIV budding.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Membrana Celular/metabolismo , Citocinesis , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Orgánulos/metabolismo , Sindecano-4/metabolismo , Sinteninas/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Ciclo Celular/genética , Membrana Celular/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Endosomas/genética , Endosomas/metabolismo , Células HeLa , Humanos , Orgánulos/genética , Unión Proteica , Sindecano-4/genética , Sinteninas/genética
10.
Cell ; 173(6): 1520-1534.e20, 2018 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-29856957

RESUMEN

The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Neuronas/fisiología , ARN , Anémonas de Mar/fisiología , Actinas/química , Secuencias de Aminoácidos , Animales , Cromatina/metabolismo , Análisis por Conglomerados , Perfilación de la Expresión Génica , Genoma , Genómica , Filogenia , Anémonas de Mar/genética , Análisis de Secuencia de ARN , Transcriptoma , Tubulina (Proteína)/química
11.
J Vis Exp ; (123)2017 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-28518119

RESUMEN

Flow cytometry has been used for the past 40 years to define and analyze the phenotype of lymphoid and other hematopoietic cells. Initially restricted to the analysis of a few fluorochromes, currently there are dozens of different fluorescent dyes, and up to 14-18 different dyes can be combined at a time. However, several limitations still impair the analytical capabilities. Because of the multiplicity of fluorescent probes, data analysis has become increasingly complex due to the need of large, multi-parametric compensation matrices. Moreover, mutant mouse models carrying fluorescent proteins to detect and trace specific cell types in different tissues have become available, so the analysis (by flow cytometry) of auto-fluorescent cell suspensions obtained from solid organs is required. Spectral flow cytometry, which distinguishes the shapes of emission spectra along a wide range of continuous wavelengths, addresses some of these problems. The data is analyzed with an algorithm that replaces compensation matrices and treats auto-fluorescence as an independent parameter. Thus, spectral flow cytometry should be capable of discriminating fluorochromes with similar emission peaks and can provide a multi-parametric analysis without compensation requirements. This protocol describes the spectral flow cytometry analysis, allowing for a 21-parameter (19 fluorescent probes) characterization and the management of an auto-fluorescent signal, providing high resolution in minor population detection. The results presented here show that spectral flow cytometry presents advantages in the analysis of cell populations from tissues difficult to characterize in conventional flow cytometry, such as the heart and the intestine. Spectral flow cytometry thus demonstrates the multi-parametric analytical capacity of high-performing conventional flow cytometry without the requirement for compensation and enables auto-fluorescence management.


Asunto(s)
Animales Modificados Genéticamente , Separación Celular/métodos , Citometría de Flujo/métodos , Proteínas Luminiscentes/genética , Animales , Colorantes Fluorescentes , Ratones
12.
PLoS One ; 11(8): e0159961, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27500930

RESUMEN

Flow cytometry, initially developed to analyze surface protein expression in hematopoietic cells, has increased in analytical complexity and is now widely used to identify cells from different tissues and organisms. As a consequence, data analysis became increasingly difficult due the need of large multi-parametric compensation matrices and to the eventual auto-fluorescence frequently found in cell suspensions obtained from solid organs. In contrast with conventional flow cytometry that detects the emission peak of fluorochromes, spectral flow cytometry distinguishes the shapes of emission spectra along a large range of continuous wave lengths. The data is analyzed with an algorithm that replaces compensation matrices and treats auto-fluorescence as an independent parameter. Thus, spectral flow cytometry should be capable to discriminate fluorochromes with similar emission peaks and provide multi-parametric analysis without compensation requirements. Here we show that spectral flow cytometry achieves a 21-parametric (19 fluorescent probes) characterization and deals with auto-fluorescent cells, providing high resolution of specifically fluorescence-labeled populations. Our results showed that spectral flow cytometry has advantages in the analysis of cell populations of tissues difficult to characterize in conventional flow cytometry, such as heart and intestine. Spectral flow cytometry thus combines the multi-parametric analytical capacity of the highest performing conventional flow cytometry without the requirement for compensation and enabling auto-fluorescence management.


Asunto(s)
Citometría de Flujo/métodos , Fluorescencia , Colorantes Fluorescentes/química , Corazón/fisiología , Intestino Delgado/metabolismo , Animales , Células Cultivadas , Femenino , Intestino Delgado/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Microesferas
13.
Cell Rep ; 14(6): 1500-1516, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26832410

RESUMEN

T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous α4ß7-expressing lymphoid progenitor compartments. αLP1 (Flt3(+)) still retains T cell potential and comprises the global ILC progenitor, while αLP2 (Flt3(-)) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of αLP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling.


Asunto(s)
Subgrupos de Linfocitos B/inmunología , Regulación del Desarrollo de la Expresión Génica , Inmunidad Innata , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Animales , Subgrupos de Linfocitos B/citología , Diferenciación Celular , Linaje de la Célula/inmunología , Proliferación Celular , Feto , Perfilación de la Expresión Génica , Proteína 2 Inhibidora de la Diferenciación/genética , Proteína 2 Inhibidora de la Diferenciación/inmunología , Integrinas/genética , Integrinas/inmunología , Ratones , Ratones Transgénicos , Receptores Notch/genética , Receptores Notch/inmunología , Análisis de la Célula Individual , Células Madre/citología , Células Madre/inmunología , Subgrupos de Linfocitos T/citología , Transcripción Genética , Transcriptoma , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/inmunología
14.
Cancer Res ; 75(22): 4753-65, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26404004

RESUMEN

Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFß1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFß1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFß1 receptor TGFßR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy.


Asunto(s)
Diferenciación Celular/fisiología , Células Madre Mesenquimatosas/patología , Osificación Heterotópica/fisiopatología , Mielofibrosis Primaria/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células Cultivadas , Femenino , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
15.
Nat Immunol ; 12(10): 949-58, 2011 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-21909092

RESUMEN

The transcription factor RORγt is required for the development of several innate lymphoid populations, such as lymphoid tissue-inducer cells (LTi cells) and cells that secrete interleukin 17 (IL-17) or IL-22. The progenitor cells as well as the developmental stages that lead to the emergence of RORγt(+) innate lymphoid cells (ILCs) remain undefined. Here we identify the chemokine receptor CXCR6 as an additional marker of the development of ILCs and show that common lymphoid progenitors lost B cell and T cell potential as they successively acquired expression of the integrin α(4)ß(7) and CXCR6. Whereas fetal RORγt(+) cells matured in the fetal liver environment, adult bone marrow-derived RORγt(+) ILCs matured outside the bone marrow, in a Notch2-dependent manner. Therefore, fetal and adult environments influence the differentiation of RORγt(+) cells differently.


Asunto(s)
Feto/inmunología , Linfocitos/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/fisiología , Receptor Notch2/fisiología , Transducción de Señal , Animales , Diferenciación Celular , Células Cultivadas , Proteínas de Unión al ADN/fisiología , Inmunidad Innata , Integrinas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores CXCR/fisiología , Receptores CXCR6
16.
J Immunol ; 183(4): 2217-21, 2009 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19635901

RESUMEN

During fetal life, CD4(+)CD3(-) lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer's patch development in mice. In adult animals, CD4(+)CD3(-) cells are found in low numbers in lymphoid organs. Whether adult CD4(+)CD3(-) cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4(+)CD3(-) cells adoptively transferred into neonatal CXCR5(-/-) mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4(+)lineage(-) cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.


Asunto(s)
Diferenciación Celular/inmunología , Interleucina-7/fisiología , Linfangiogénesis/inmunología , Tejido Linfoide/inmunología , Tejido Linfoide/metabolismo , Receptores de Ácido Retinoico/biosíntesis , Receptores de Hormona Tiroidea/biosíntesis , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/genética , Células Cultivadas , Feto/citología , Feto/inmunología , Feto/metabolismo , Interleucina-7/biosíntesis , Interleucina-7/deficiencia , Linfangiogénesis/genética , Tejido Linfoide/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Receptores de Ácido Retinoico/deficiencia , Receptores de Ácido Retinoico/fisiología , Receptores de Hormona Tiroidea/deficiencia , Receptores de Hormona Tiroidea/fisiología , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Subgrupos de Linfocitos T/citología
17.
Swiss Med Wkly ; 138(35-36): 500-5, 2008 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-18792823

RESUMEN

Chronic inflammatory diseases such as rheumatoid arthritis (RA) are associated with the de novo formation of organised lymphoid tissue in a subpopulation of patients. The aberrant expression of cytokines and chemokines by stromal cells plays an important role in recruitment and survival of effector cells of the immune system and the development of ectopic tertiary lymphoid organs (TLOs). TLOs may promote the persistence of inflammation and the recognition of self antigens. Recent studies in man and mice now indicate that interleukin 7 (IL-7) is implicated in the formation of TLOs and progression of chronic inflammation.


Asunto(s)
Artritis Reumatoide/fisiopatología , Desarrollo Fetal , Interleucina-7/fisiología , Tejido Linfoide/crecimiento & desarrollo , Animales , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Humanos , Tejido Linfoide/inmunología , Ratones , Células del Estroma/inmunología
18.
Immunity ; 26(5): 643-54, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17521585

RESUMEN

Development of Peyer's patches and lymph nodes requires the interaction between CD4+ CD3- IL-7Ralpha+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells. Here we showed that by promoting their survival, enhanced expression of interleukin-7 (IL-7) in transgenic mice resulted in accumulation of LTi cells. With increased IL-7 availability, de novo formation of VCAM-1+ Peyer's patch anlagen occurred along the entire fetal gut resulting in a 5-fold increase in Peyer's patch numbers. IL-7 overexpression also led to formation of multiple organized ectopic lymph nodes and cecal patches. After immunization, ectopic lymph nodes developed normal T cell-dependent B cell responses and germinal centers. Mice overexpressing IL-7 but lacking either RORgamma, a factor required for LTi cell generation, or lymphotoxin alpha1beta2 had neither Peyer's patches nor ectopic lymph nodes. Therefore, by controlling LTi cell numbers, IL-7 can regulate the formation of both normal and ectopic lymphoid organs.


Asunto(s)
Diferenciación Celular/inmunología , Interleucina-7/metabolismo , Tejido Linfoide/citología , Tejido Linfoide/metabolismo , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/metabolismo , Animales , Supervivencia Celular , Células Cultivadas , Feto/metabolismo , Regulación de la Expresión Génica , Interleucina-7/genética , Tejido Linfoide/inmunología , Ratones , Ratones Transgénicos , Células Madre/citología , Células Madre/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Molécula 1 de Adhesión Celular Vascular/metabolismo
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