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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901471v1 183/8/5251    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Jones, T. G. Articles by Gurish, M. F. PubMed PubMed Citation Articles by Jones, T. G. Articles by Gurish, M. F.

Antigen-Induced Increases in Pulmonary Mast Cell Progenitor Numbers Depend on IL-9 and CD1d-Restricted NKT Cells¹

Tatiana G. Jones,^* Jenny Hallgren,^2* Alison Humbles, Timothy Burwell, Fred D. Finkelman, Pilar Alcaide, K. Frank Austen,^* and Michael F. Gurish^3*

^*Division of Rheumatology, Immunology and Allergy and Center for Excellence in Vascular Biology, Department of Pathology, Brigham & Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115; Department of Autoimmunity and Inflammation, MedImmune, Inc., Gaithersburg, MD, 20878; and Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220

Pulmonary mast cell progenitor (MCp) numbers increase dramatically in sensitized and aerosolized Ag-challenged mice. This increase depends on CD4⁺ T cells, as no MCp increase occurs in the lungs of sensitized wild-type (WT) mice after mAb depletion of CD4⁺ but not CD8⁺ cells before aerosol Ag challenge. Neither the genetic absence of IL-4, IL-4R chain, STAT-6, IFN-, or IL-12p40 nor mAb blockade of IFN-, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-12p40, or IL-12p40Rβ1 before Ag challenge in WT mice reduces the pulmonary MCp increase. However, sensitized and Ag-challenged IL-9-deficient mice and sensitized WT mice given mAb to IL-9 just before Ag challenge show significant reductions in elicited lung MCp/10⁶ mononuclear cells of 47 and 66%, respectively. CD1d-deficient mice and WT mice receiving anti-CD1d before Ag challenge also show significant reductions of 65 and 59%, respectively, in elicited lung MCp/10⁶ mononuclear cells, revealing an additional requirement for MCp recruitment. However, in J18-deficient mice, which lack only type 1 or invariant NKT cells, the increase in the numbers of lung MCp with Ag challenge was intact, indicating that their recruitment must be mediated by type 2 NKT cells. Furthermore, anti-CD1d treatment of IL-9-deficient mice or anti-IL-9 treatment of CD1d-deficient mice does not further reduce the significant partial impairment of MCp recruitment occurring with a single deficiency. These findings implicate type 2 NKT cells and IL-9 as central regulators that function in the same pathway mediating the Ag-induced increase in numbers of pulmonary MCp.

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 Grants AI 031599, HL 036110, HL 076383, HL36028, and HL53993 from the National Institutes of Health, a Merit Award from the U.S. Department of Veterans Affairs (to F.D.F.), and a grant from the MedImmune Inc. (to M.F.G.).

² Current address: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.

³ Address correspondence and reprint requests to Dr. Michael F. Gurish, Brigham and Women’s Hospital, Smith Research Building, Room 616, One Jimmy Fund Way, Boston, MA, 02115. E-mail address: mgurish{at}rics.bwh.harvard.edu

⁴ Abbreviations used in this paper: MC, mast cell; DC, dendritic cell; -GalCer, -galactosylceramide; MCp, MC progenitor; MNC, mononuclear cell; Treg, regulatory T; SCF, stem cell factor; WT, wild type; iNKT, invariant NKT.