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Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis

Françozo, Marcela C S ; Costa, Frederico R C ; Guerra-Gomes, Isabel C ; Silva, João S ; Sesti-Costa, Renata

Scientific reports, 2019-10, Vol.9 (1), p.14766-11, Article 14766 [Periódico revisado por pares]

England: Nature Publishing Group

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Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis
Autor: Françozo, Marcela C S ; Costa, Frederico R C ; Guerra-Gomes, Isabel C ; Silva, João S ; Sesti-Costa, Renata
Assuntos: Adoptive transfer ; Animals ; CCL17 protein ; CD4 antigen ; CD8 antigen ; Cell activation ; Cell adhesion & migration ; Cell Movement ; Chemokine CCL17 - immunology ; Chronic infection ; Coxsackievirus Infections - complications ; Coxsackievirus Infections - immunology ; Coxsackievirus Infections - pathology ; Coxsackieviruses ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Enterovirus B, Human - immunology ; Heart diseases ; Immunoregulation ; Infections ; Interleukin 12 ; Leukocyte migration ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Mice, Inbred C57BL ; Myocarditis ; Pancreas ; Pancreatitis ; Pancreatitis - etiology ; Pancreatitis - immunology ; Pancreatitis - pathology ; Pancreatitis - virology ; Receptors, CCR4 - immunology ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology ; β-Interferon ; γ-Interferon
É parte de: Scientific reports, 2019-10, Vol.9 (1), p.14766-11, Article 14766
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Type B coxsackieviruses (CVB) are enteroviruses responsible for a common infectious myocarditis and pancreatitis. DCs and regulatory T cells (Tregs) are key players in controlling virus replication and regulating the immune response and tissue damage, respectively. However, the mechanisms underlying cellular migration to target tissues remain unclear. In the present study, we found that CVB5 infection induced CCL17 production and controlled the migration of CCR4 DCs and CCR4 Tregs to the pancreatic lymph nodes (pLN). CVB5 infection of CCR4 mice reduced the migration of the CD8α DC subset and reduced DC activation and production of IFN-β and IL-12. Consequently, CCR4 mice presented decreased IFN-γ-producing CD4 and CD8 T cells, an increased viral load and more severe pancreatitis. In addition, CCR4 mice had impaired Treg accumulation in pLN as well as increased T lymphocyte activation. Adoptive transfer of CCR4 Tregs but not CCR4 Tregs was able to regulate T lymphocyte activation upon CVB5 infection. The present data reveal a previously unknown role for CCR4 in coordinating immune cell migration to CVB-infected tissues and in controlling subsequent pancreatitis. These new insights may contribute to the design of future therapies for acute and chronic infection of non-polio enteroviruses.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis

Françozo, Marcela C S ; Costa, Frederico R C ; Guerra-Gomes, Isabel C ; Silva, João S ; Sesti-Costa, Renata

England: Nature Publishing Group

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