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CD11b⁺ Myeloid Cells Are the Key Mediators of Th2 Cell Homing into the Airway in Allergic Inflammation¹

Benjamin D. Medoff^*,, Edward Seung^*, Sandra Hong^*, Seddon Y. Thomas^*, Barry P. Sandall^*,, Jeremy S. Duffield, Douglas A. Kuperman, David J. Erle^¶ and Andrew D. Luster^2,*

^* Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129; Pulmonary and Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Renal Division and Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and ^¶ Lung Biology Center, Department of Medicine, Cardiovascular Research Institute, and Program in Immunology, University of California, San Francisco, CA 94143

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants K08 HL072775 (to B.D.M.) and R37 AI40618 (to A.D.L.).

² Address correspondence and reprint requests to Dr. Andrew D. Luster, Massachusetts General Hospital, CNY 8301, 149 13th Street Charlestown, MA 02129. E-mail address: aluster{at}mgh.harvard.edu

³ Abbreviations used in this paper: AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; DT, diphtheria toxin; DTR, DT receptor; PAS, Periodic-Acid-Schiff.

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The JI 2009 182: 1-2. [Full Text]