title: Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation.
abstract: BACKGROUND
  Induction of endogenous regulatory T (Treg) cells represents an exciting new potential modality for treating allergic diseases, such as asthma. Treg cells have been implicated in the regulation of asthma, but the anatomic location in which they exert their regulatory function and the mechanisms controlling the migration necessary for their suppressive function in asthma are not known. Understanding these aspects of Treg cell biology will be important for harnessing their power in the clinic.
  
  
  OBJECTIVE
  We sought to determine the anatomic location at which Treg cells exert their regulatory function in the sensitization and effector phases of allergic asthma and to determine the chemokine receptors that control the migration of Treg cells to these sites in vivo in both mice and human subjects.
  
  
  METHODS
  The clinical efficacy and anatomic location of adoptively transferred chemokine receptor-deficient CD4(+)CD25(+) forkhead box protein 3-positive Treg cells was determined in the sensitization and effector phases of allergic airway inflammation in mice. The chemokine receptor expression profile was determined on Treg cells recruited into the human airway after bronchoscopic segmental allergen challenge of asthmatic patients.
  
  
  RESULTS
  We show that CCR7, but not CCR4, is required on Treg cells to suppress allergic airway inflammation during the sensitization phase. In contrast, CCR4, but not CCR7, is required on Treg cells to suppress allergic airway inflammation during the effector phase. Consistent with our murine studies, human subjects with allergic asthma had an increase in CCR4-expressing functional Treg cells in the lungs after segmental allergen challenge.
  
  
  CONCLUSIONS
  The location of Treg cell function differs during allergic sensitization and allergen-induced recall responses in the lung, and this differential localization is critically dependent on differential chemokine function.
authors: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors: Roshi
authors: R
authors: Afshar
authors: James P
authors: JP
authors: Strassner
authors: Edward
authors: E
authors: Seung
authors: Benjamin
authors: B
authors: Causton
authors: Josalyn L
authors: JL
authors: Cho
authors: R Scott
authors: RS
authors: Harris
authors: Daniel L
authors: DL
authors: Hamilos
authors: Benjamin D
authors: BD
authors: Medoff
authors: Andrew D
authors: AD
authors: Luster
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D054398:Receptors, CCR4 / Q000172:deficiency / Q000235:genetics; D054400:Receptors, CCR7 / Q000172:deficiency / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D018925:Chemokines; D054398:Receptors, CCR4; D054400:Receptors, CCR7
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