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XCL1 Enhances Regulatory Activities of CD4⁺CD25^highCD127^low/– T Cells in Human Allergic Asthma¹

Khoa D. Nguyen^*, Alison Fohner^*, Jerome D. Booker^*, Chen Dong^*, Alan M. Krensky and Kari C. Nadeau^2,*

^* Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305; and Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892

Chemokine-mediated recruitment of regulatory cell subsets to the airway during inflammation and enhancement of their activities are potential strategies for therapeutic development in allergic asthma (AA). In this study, we aim to explore the role of XCL1, a chemokine associated with immune suppression and allergy, on CD4⁺CD25^highCD127^low/– regulatory T cell (Treg) function in AA. Flow cytometry and PCR analysis showed a reduction in XCL1 and XCR1 expression in AA Treg compared with healthy control and nonallergic asthmatic counterparts. This reduction in XCL1 expression was associated with the suboptimal regulatory function of Treg in AA. Interestingly, incubation with recombinant human XCL1 significantly increased Treg-mediated suppression and cytotoxicity by up-regulating expression of XCL1 and chief effector molecules of Treg function. Altogether, these results suggest an association between dysregulated XCL1 expression and reduced Treg activities in AA, as well as a potential role of XCL1 in reversing defective Treg function in the disease.

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 from the Mary Hewitt Loveless Foundation and the Parker B. Francis Foundation.

² Address correspondence and reprint requests to Dr. Kari C. Nadeau, Department of Pediatrics, Stanford University, Stanford, CA, 94305. E-mail address: knadeau{at}stanford.edu

³ Abbreviations used in the article: Treg, regulatory T cell; AA, allergic asthma; HC, healthy control; FEV₁, forced expiratory volume in 1 s; NA, nonallergic asthmatic; BAL, bronchoalveolar lavage fluid; MFI, mean fluorescent intensity; OCS, oral corticosteroid; 7-AAD, 7-aminoactinomycin D; QT-PCR, quantitative PCR.

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				K. D. Nguyen, C. Vanichsarn, and K. C. Nadeau Impaired IL-10-dependent Induction of Tolerogenic Dendritic Cells by CD4+CD25hiCD127lo/- Natural Regulatory T Cells in Human Allergic Asthma Am. J. Respir. Crit. Care Med., November 1, 2009; 180(9): 823 - 833. [Abstract] [Full Text] [PDF]