CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in allergic inflammation.
STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into the airways in allergic pulmonary inflammation, and thus is a potential therapeutic target in asthma. However, the critical cellular source of STAT6-mediated chemokine production has not been defined. In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung identified these cells as the critical cellular source for the chemokines CCL17 and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help orchestrate the adaptive immune response in asthma, in part, through the production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes into the airway.
Medoff
Benjamin D
BD
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Seung
Edward
E
Hong
Sandra
S
Thomas
Seddon Y
SY
Sandall
Barry P
BP
Duffield
Jeremy S
JS
Kuperman
Douglas A
DA
Erle
David J
DJ
Luster
Andrew D
AD
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000096:biosynthesis*; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000096:biosynthesis; D054422:Chemokine CCL22 / Q000096:biosynthesis; D054423:Chemokine CCL24 / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D039481:CD11b Antigen; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; C515485:Ccl24 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054423:Chemokine CCL24; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D010047:Ovalbumin