Regulatory T cells migrate to airways via CCR4 and attenuate the severity of airway allergic inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Univ São Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 São Paulo, Brazil Univ São Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil Universidade Federal de São Paulo, São Paulo Sch Med, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, São Paulo Sch Med, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Web of Science