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

Autor(es)

Francozo, Marcela C. S. ^[1] ; Costa, Frederico R. C. ^[2] ; Guerra-Gomes, Isabel C. ^[2] ; Silva, Joao S. ^{[2, 3]} ; Sesti-Costa, Renata ^[4]

Afiliação do(s) autor(es)

^[1] Hannover Med Sch, Inst Pathol, Hannover - Germany

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil

^[3] FIOCRUZ Bi Inst Translat Med Project, Ribeirao Preto, SP - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Hematol Ctr, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, OCT 14 2019.
• Citações Web of Science: 0

Resumo

Type B coxsackieviruses (CVB) are enteroviruses responsible for a common infectious myocarditis and pancreatitis. DCs and regulatoryT 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 CD8 alpha(+) DC subset and reduced DC activation and production of IFN-beta and IL-12. Consequently, CCR4(-/- )mice presented decreased IFN-gamma-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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/15832-6 - Papel do CCR4 na pancreatite experimental induzida pelo vírus coxsackie B5
• Beneficiário: Marcela Cristina Santiago Françozo
• Modalidade de apoio: Bolsas no Brasil - Mestrado