Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Francozo, Marcela C. S. [1] ; Costa, Frederico R. C. [2] ; Guerra-Gomes, Isabel C. [2] ; Silva, Joao S. [2, 3] ; Sesti-Costa, Renata [4]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, OCT 14 2019.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/15832-6 - Effect of CCR4 in coxsackievirus B5-induced pancreatitis experimental
Grantee:Marcela Cristina Santiago Françozo
Support type: Scholarships in Brazil - Master