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A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract¹

Naiqian Niu^2,*, Marc K. Le Goff^2,*, Fangyong Li^*, Marina Rahman^*, Robert J. Homer and Lauren Cohn^3,*

^* Section of Pulmonary and Critical Care Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520

In animals with acute airway inflammation followed by repeated exposure to inhaled Ag, inflammation wanes over time and thus limits the study of chronic airway inflammatory diseases such as asthma. We developed a model of airway inflammation and inhalational exposure to investigate regulatory pathways in the respiratory tract. We show that Th1- and Th2-induced airway inflammation followed by repeated exposure to inhaled Ag leads to a state of immunosuppression. Challenge of these animals with a marked population of TCR transgenic effector Th1 or Th2 cells results in a striking inhibition of inflammation and effector Th cells. In Th2 models, airway hyperresponsiveness, mucus, and eosinophilia are reduced. The inhibitory effects observed are Ag nonspecific, can be induced in lymphocyte-deficient mice, and are associated with a population of TGF-1-expressing macrophages. Induction of this pathway may offer potent localized treatment of chronic T cell-mediated respiratory illnesses and provide insights into the development of such diseases.

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 Grant R01-HL64040 (to L.C.) and an American Lung Association Career Investigator Award (to L.C.).

² N.N. and M.K.L.G. contributed equally to this publication.

³ Address correspondence and reprint requests to Dr. Lauren Cohn, Section of Pulmonary and Critical Care, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208057, New Haven, CT 06520. E-mail address: lauren.cohn{at}yale.edu

⁴ Abbreviations used in this paper: IT, inhaled tolerance; AHR, airway hyperresponsiveness; AIRID, airway inflammation-related inhibition of disease; BAL, bronchoalveolar lavage; HDM, house dust mite; KLH, keyhole limpet hemocyanin; inh-KLH, inhaled KLH; inh-OVA, inhaled OVA; PAS, periodic acid-Schiff; MCh, methacholine; MSC, myeloid suppressor cell; pOVA^323–339, OVA peptide 323–339; Tg, transgenic; Treg, regulatory T cell.

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				C. L. Van Hove, T. Maes, G. F. Joos, and K. G. Tournoy Comment on "A Novel Pathway that Regulates Inflammatory Disease in the Respiratory Tract" J. Immunol., June 15, 2007; 178(12): 7501 - 7501. [Full Text] [PDF]

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