Among the mechanisms of suppression that T regulatory (Treg) cells exert to control the immune responses, the secretion of small extracellular vesicles (sEV) has been recently proposed as a novel contact‐independent immunomodulatory mechanism. Previous studies have demonstrated that Treg cells produce sEV, including exosomes, able to modulate the effector function of CD4+ T cells, and antigen presenting cells (APCs) such as dendritic cells (DCs) through the transfer of microRNA, cytokines, the production of adenosine, among others. Previously, we have demonstrated that Neuropilin‐1 (Nrp1) is required for Tregs‐mediated immunosuppression mainly by impacting on the phenotype and function of effector CD4+ T cells. Here, we show that Foxp3+ Treg cells secrete sEV, which bear Nrp1 in their membrane. These sEV modulate effector CD4+ T cell phenotype and proliferation in vitro in a Nrp1‐dependent manner. Proteomic analysis indicated that sEV obtained from wild type (wt) and Nrp1KO Treg cells differed in proteins related to immune tolerance, finding less representation of CD73 and Granzyme B in sEV obtained from Nrp1KO Treg cells. Likewise, we show that Nrp1 is required in Treg cell‐derived sEV for inducing skin transplantation tolerance, since a reduction in graft survival and an increase on M1/M2 ratio were found in animals treated with Nrp1KO Treg cell‐derived sEV. Altogether, this study describes for the first time that Treg cells secrete sEV containing Nrp1 and that this protein, among others, is necessary to promote transplantation tolerance in vivo via sEV local administration.
FRISBEE RESUMENIntroducción: En dentición primaria, la pulpotomía con formocresol ha sido convencionalmente utilizada para el tratamiento de caries cercanas a la pulpa. Sin embargo, la seguridad de este material ha sido cuestionada. Por otro lado, el biodentine ha sido propuesto como un biomaterial sustituto bioactivo de la dentina, pero no está clara su efectividad. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y una tabla GRADE para el resumen de los resultados. Resultados y conclusiones: Identificamos tres revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos correspondientes a ensayos aleatorizados. Concluimos que no se puede establecer con claridad si biodentine comparado con formocresol aumenta el éxito clínico y el éxito radiográfico en pulpotomía en pacientes con dentición primaria, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.
The microbiome corresponds to the genetic component of microorganisms (archaea, bacteria, phages, viruses, fungi, and protozoa) that coexist with an individual. During the last two decades, research on this topic has become massive demonstrating that in both homeostasis and disease, the microbiome plays an important role, and in some cases, a decisive one. To date, microbiota have been identified at different body locations, such as the eyes, lung, gastrointestinal and genitourinary tracts, and skin, and technological advances have permitted the taxonomic characterization of resident species and their metabolites, in addition to the cellular and molecular components of the host that maintain a crosstalk with local microorganisms. Here, we summarize recent studies regarding microbiota residing in different zones of the body and their relationship with the immune system. We emphasize the immune components underlying pathological conditions and how they interact with local (and distant) microbiota.
The suppressive function of T-regulatory cells (Tregs) can have a detrimental effect on immune responses against tumor cells. Within the Treg cells subset, a new non-classical population has been reported, which expresses high levels of CD49b molecule and, depending on their activation status, can also express the canonical Tregs transcription factor Foxp3. In this report, we sought to characterize Tregs subsets in a murine melanoma model and disrupt the CD49b/CD29 axis by administering an anti-CD29 antibody in tumor-bearing mice. Our data shows that whereas in the draining lymph nodes, the Tr1 cells subset composes <5% of CD4+ T cells, in the tumor, they reach ∼30% of CD4+ T cells. Furthermore, Tr1 cells share the expression of suppressive molecules, such as Nrp-1, PD-1, and CD73, which are highly expressed on Tr1 cells found in tumor-infiltrating leukocytes (TILs). Regardless of the phenotypic similarities with cTreg cells, Tr1 cells display a low proliferative activity, as shown in the kinetics and the incorporation of 5-bromodeoxyuridine (BrdU) experiments. With the intent to impact on Tr1 cells, we administered anti-CD29 antibody into tumor mice, observing that the treatment effectively inhibits tumor growth. This effect is at least mediated by the enrichment of pro-inflammatory T cells, including IFN-γ+ cTreg and IFN-γ+ Tr1 cells (with reduced expression of IL-10), plus Th1 and Tc cells. In this study, we present Tr1 cell characterization in tumor-bearing animals and introduce CD29 as a target for tumor therapy, supported by a meta-analysis indicating that CD29 is present in human biopsies.
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