Author | Inkeles, Megan S. | |
Author | Teles, Rosane M. B. | |
Author | Pouldar, Delila | |
Author | Andrade, Priscila R. | |
Author | Madigan, Cressida A. | |
Author | Lopez, David | |
Author | Ambrose, Mike | |
Author | Noursadeghi, Mahdad | |
Author | Sarno, Euzenir N. | |
Author | Rea, Thomas H. | |
Author | Ochoa, Maria T. | |
Author | Iruela-Arispe, M Luisa | |
Author | Swindell, William R. | |
Author | Ottenhoff, Tom H. M. | |
Author | Geluk, Annemieke | |
Author | Bloom, Barry R. | |
Author | Pellegrini, Matteo | |
Author | Modlin, Robert L. | |
Access date | 2017-02-21T11:30:39Z | |
Available date | 2017-02-21T11:30:39Z | |
Document date | 2016 | |
Citation | INKELES, Megan S. et al. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy. JCI Insight, v.1, n.15, e88843, 16p, sept. 2016. | pt_BR |
ISSN | 2379-3708 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/17861 | |
Language | eng | pt_BR |
Publisher | American Society for Clinical Investigation | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Hanseníase | pt_BR |
Subject in Portuguese | Deconvolução de tipo celular | pt_BR |
Subject in Portuguese | Vias imunológicas | pt_BR |
Subject in Portuguese | Redes genéticas | pt_BR |
Subject in Portuguese | Defesas do hospedeiro | pt_BR |
Title | Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy | pt_BR |
Type | Article | pt_BR |
DOI | 10.1172/jci.insight.88843 | |
Abstract | Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA. | pt_BR |
Affilliation | University College London. Division of Infection and Immunity. London, United Kingdom. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | University of Southern California School of Medicine. Department of Dermatology. Los Angeles, CA, USA. | pt_BR |
Affilliation | University of Southern California School of Medicine. Department of Dermatology. Los Angeles, CA, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA. | pt_BR |
Affilliation | University of Michigan School of Medicine. Department of Dermatology. Ann Arbor, Michigan, USA. | pt_BR |
Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
Affilliation | Harvard School of Public Health. Boston, Massachusetts, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA. | pt_BR |
Affilliation | David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA / UCLA. Department of Microbiology, Immunology and Molecular Genetics. Los Angeles, California, USA | pt_BR |
Subject | Leprosy | pt_BR |
Subject | immune pathways | pt_BR |
Subject | Cell-type deconvolution | pt_BR |
Subject | host defense | pt_BR |
Subject | immune pathways | pt_BR |
Subject | gene networks | pt_BR |