Regulatory T Cells Migrate to Airways via CCR4 and Attenuate the Severity of Airway Allergic Inflammation

Regulatory T Cells Migrate to Airways via CCR4 and Attenuate the Severity of Airway Allergic Inflammation

Autor Faustino, Lucas Google Scholar
Fonseca, Denise Morais da Google Scholar
Takenaka, Maisa Carla Silveira Autor UNIFESP Google Scholar
Mirotti, Luciana Google Scholar
Florsheim, Esther Borges Google Scholar
Guereschi, Marcia Grando Autor UNIFESP Google Scholar
Silva, Joao Santana Google Scholar
Basso, Alexandre Salgado Autor UNIFESP Google Scholar
Russo, Momtchilo Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo We have previously shown that regulatory T (Treg) cells that accumulate in the airways of allergic mice upregulate CC-chemokine receptor 4 (CCR4) expression. These Treg cells suppressed in vitro Th2 cell proliferation but not type 2 cytokine production. in the current study, using a well-established murine model of allergic lung disease or oral tolerance, we evaluated the in vivo activity of Treg cells in allergic airway inflammation with special focus on CCR4 function. We found that allergic, but not tolerant, mice treated with anti-CD25 Ab showed increased airway eosinophilia and IL-5- or IL-4-producing Th2 cells when compared with untreated mice. Notably, mice with CCR4 deficiency displayed an augmented airway allergic inflammation compared with wild-type or CCR2 knockout (KO) mice. the allergic phenotype of CCR4KO mice was similar to that observed in anti-CD25-treated mice. the exacerbated allergic inflammation of CCR4KO mice was directly associated with an impaired migration of Treg cells to airways and augmented frequency of pulmonary Th2 cells. Adoptive transfer of CD25(+) CD4(+) T cells expressing high levels of CCR4, but not CCR4KO CD25(+) CD4(+) T cells, attenuated the severe airway Th2 response of CCR4KO mice. Our results show that CCR4 is critically involved in the migration of Treg cells to allergic lungs that, in turn, attenuate airway Th2 activation and allergic eosinophilic inflammation. the Journal of Immunology, 2013, 190: 2614-2621.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Data de publicação 2013-03-15
Publicado em Journal of Immunology. Bethesda: Amer Assoc Immunologists, v. 190, n. 6, p. 2614-2621, 2013.
ISSN 0022-1767 (Sherpa/Romeo, fator de impacto)
Publicador Amer Assoc Immunologists
Extensão 2614-2621
Fonte http://dx.doi.org/10.4049/jimmunol.1202354
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000315657200019
Endereço permanente http://repositorio.unifesp.br/handle/11600/36087

Exibir registro completo




Arquivo

Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta