Regulatory T Cells Migrate to Airways via CCR4 and Attenuate the Severity of Airway Allergic Inflammation
Open Access
- 15 March 2013
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 190 (6), 2614-2621
- https://doi.org/10.4049/jimmunol.1202354
Abstract
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.This publication has 54 references indexed in Scilit:
- Regulatory T Cells Accumulate in the Lung Allergic Inflammation and Efficiently Suppress T-Cell Proliferation but Not Th2 Cytokine ProductionClinical and Developmental Immunology, 2011
- In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti‐CD25 monoclonal antibody is mediated by FcγRIII+ phagocytesEuropean Journal of Immunology, 2010
- Anti-Siglec-F Antibody Reduces Allergen-Induced Eosinophilic Inflammation and Airway RemodelingPublished by The American Association of Immunologists ,2009
- Contribution of CCR4 and CCR8 to antigen-specific TH2 cell trafficking in allergic pulmonary inflammationJournal of Allergy and Clinical Immunology, 2008
- Orchestrating the orchestrators: chemokines in control of T cell trafficNature Immunology, 2008
- Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthmaThe Journal of Experimental Medicine, 2008
- Altering the distribution of Foxp3+ regulatory T cells results in tissue-specific inflammatory diseaseThe Journal of Experimental Medicine, 2007
- CCR4-dependent regulatory T cell function in inflammatory bowel diseaseThe Journal of Experimental Medicine, 2007
- Preferential expression of Th2-type chemokine and its receptor in atopic dermatitisInternational Immunology, 2002
- Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune EncephalomyelitisScience, 1994