RESUMO
Recently it was shown that circulating Ly6C(+) monocytes traffic from tissue to the draining lymph nodes (LNs) with minimal alteration in their overall phenotype. Furthermore, in the steady state, Ly6C(+) monocytes are as abundant as classical dendritic cells (DCs) within the draining LNs, and even more abundant during inflammation. However, little is known about the functional roles of constitutively trafficking Ly6C(+) monocytes. In this study we investigated whether Ly6C(+) monocytes can efferocytose (acquire dying cells) and cross-present cell-associated antigen, a functional property particularly attributed to Batf3(+) DCs. We demonstrated that Ly6C(+) monocytes intrinsically efferocytose and cross-present cell-associated antigen to CD8(+) T cells. In addition, efferocytosis was enhanced upon direct activation of the Ly6C(+) monocytes through its corresponding TLRs, TLR4 and TLR7. However, only ligation of TLR7, and not TLR4, enhanced cross-presentation by Ly6C(+) monocytes. Overall, this study outlines two functional roles, among others, that Ly6C(+) monocytes have during an adaptive immune response.
Assuntos
Antígenos Ly/metabolismo , Monócitos/metabolismo , Animais , Apoptose/efeitos da radiação , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Confocal , Monócitos/citologia , Ovalbumina/imunologia , Fagocitose , RNA/química , RNA/metabolismo , Proteínas Repressoras/metabolismo , Análise de Sequência de RNA , Baço/citologia , Baço/imunologia , Timócitos/citologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Transcriptoma , Raios UltravioletaRESUMO
Gene expression array technology has made possible the assay of expression levels of tens of thousands of genes at a time; large databases of such measurements are currently under construction. One important use of such databases is the ability to search for experiments that have similar gene expression levels as a query, potentially identifying previously unsuspected relationships among cellular states. Such searches depend crucially on the metric used to assess the similarity between pairs of experiments. The complex joint distribution of gene expression levels, particularly their correlational structure and non-normality, make simple similarity metrics such as Euclidean distance or correlational similarity scores suboptimal for use in this application. We present a similarity metric for gene expression array experiments that takes into account the complex joint distribution of expression values. We provide a computationally tractable approximation to this measure, and have implemented a database search tool based on it. We discuss implementation issues and efficiency, and we compare our new metric to other standard metrics.
Assuntos
Perfilação da Expressão Gênica/estatística & dados numéricos , Software , Teorema de Bayes , Biologia Computacional , Bases de Dados Genéticas , Genes Fúngicos , Saccharomyces cerevisiae/genéticaRESUMO
An analogue of the 10 C-terminal amino acids of neuropeptide Y (NPY) containing three D-isomeric substitutions (27-36-D) has been synthesized and its cardiovascular activity studied in Sprague-Dawley (SD) and spontaneously hypertensive (SHR) rats. Intravenous administration of 1000 nmol/kg 27-36-D decreases MAP in SHR (-59.9 +/- 5.0 mmHg) and SD rats (-44.4 +/- 4.7 mmHg). The hypotension produced by 1000 nmol/kg 27-36-D diminished by 71.2% following pretreatment with the histamine receptor antagonist diphenhydramine, although histamine depletion with compound 48/80 does not significantly alter this hypotension. These data suggest that NPY (27-36)-D produces a profound and sustained hypotension in two strains of rat which is partially attributable to activity at histamine receptors.