Publicação
Innate regulation of granulomatous inflammation in sarcoidosis
| Resumo: | Sarcoidosis is a systemic inflammatory disease of unknow etiology characterized by the presence of non-caseating granulomas, with lung involvement in almost all cases. Although the histological landscape of human sarcoid granulomas has been extensively studied, the genetic, molecular and inflammatory signatures underlying macrophage transformation into epithelioid cells that aggregate, initiate and sustain granulomatous inflammation remain elusive. Consequently, available treatment options are scarce and currently, there are no therapeutic approaches targeting pathogenic mechanisms in sarcoidosis. Guided by its pivotal immunoregulatory role at the crossroads of inflammation, or hypothesis is that the long pentraxin-3 (PTX3) acts as a central regulatory node in sarcoidosis by controlling leukocyte recruitment and granuloma formation, and consequently, impacting disease course and outcome. By resorting to a murine model of granulomatous inflammation, we identified PTX3 as an integral component of sarcoid granulomas and a candidate factor controlling inflammation in sarcoidosis. Moreover, we revealed an association between loss-of-function genetic variants in the PTX3 gene and the risk of developing sarcoidosis. Accordingly, PTX3 deficiency was accompanied by an increased leukocyte trafficking to the pulmonary microenvironment of these patients. In toto, our results are expected to provide crucial insights into the field of pulmonary medicine, opening new horizons and laying the foundations for personalized medical interventions in sarcoidosis. |
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| Autores principais: | Campos, Ana Cláudia Ferreira |
| Assunto: | Ciências Médicas |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Sarcoidosis is a systemic inflammatory disease of unknow etiology characterized by the presence of non-caseating granulomas, with lung involvement in almost all cases. Although the histological landscape of human sarcoid granulomas has been extensively studied, the genetic, molecular and inflammatory signatures underlying macrophage transformation into epithelioid cells that aggregate, initiate and sustain granulomatous inflammation remain elusive. Consequently, available treatment options are scarce and currently, there are no therapeutic approaches targeting pathogenic mechanisms in sarcoidosis. Guided by its pivotal immunoregulatory role at the crossroads of inflammation, or hypothesis is that the long pentraxin-3 (PTX3) acts as a central regulatory node in sarcoidosis by controlling leukocyte recruitment and granuloma formation, and consequently, impacting disease course and outcome. By resorting to a murine model of granulomatous inflammation, we identified PTX3 as an integral component of sarcoid granulomas and a candidate factor controlling inflammation in sarcoidosis. Moreover, we revealed an association between loss-of-function genetic variants in the PTX3 gene and the risk of developing sarcoidosis. Accordingly, PTX3 deficiency was accompanied by an increased leukocyte trafficking to the pulmonary microenvironment of these patients. In toto, our results are expected to provide crucial insights into the field of pulmonary medicine, opening new horizons and laying the foundations for personalized medical interventions in sarcoidosis. |
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