XCL1 enhances regulatory activities of CD4+CD25highCD127low/- T cells in human allergic asthma

被引:44
作者
Nguyen, Khoa D. [1 ]
Fohner, Alison [1 ]
Booker, Jerome D. [1 ]
Dong, Chen [1 ]
Krensky, Alan M. [2 ]
Nadeau, Kari C. [1 ]
机构
[1] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA
[2] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA
关键词
D O I
10.4049/jimmunol.181.8.5386
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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(high)CD127(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.
引用
收藏
页码:5386 / 5395
页数:10
相关论文
共 34 条
[1]   Role of regulatory T cells in allergy and asthma [J].
Akbari, O ;
Stock, P ;
DeKruyff, RH ;
Umetsu, DT .
CURRENT OPINION IN IMMUNOLOGY, 2003, 15 (06) :627-633
[2]   ACTIVATION OF DUAL T-CELL SIGNALING PATHWAYS BY THE CHEMOKINE RANTES [J].
BACON, KB ;
PREMACK, BA ;
GARDNER, P ;
SCHALL, TJ .
SCIENCE, 1995, 269 (5231) :1727-1730
[3]   Human CD4+CD25+ regulatory T cells [J].
Baecher-Allan, C ;
Viglietta, V ;
Hafler, DA .
SEMINARS IN IMMUNOLOGY, 2004, 16 (02) :89-97
[4]   Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production [J].
Bellinghausen, I ;
Klostermann, B ;
Knop, J ;
Saloga, J .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 111 (04) :862-868
[5]   Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway [J].
Castro, M ;
Bloch, SR ;
Jenkerson, MV ;
DeMartino, S ;
Hamilos, DL ;
Cochran, RB ;
E, XP ;
Zhang, LA ;
Wang, HC ;
Bradley, JP ;
Schechtman, KB ;
Holtzman, MJ .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (07) :842-849
[6]   The C-class chemokine lymphotactin costimulates the apoptosis of human CD4+ T cells [J].
Cerdan, C ;
Devilard, E ;
Xerri, L ;
Olive, D .
BLOOD, 2001, 97 (08) :2205-2212
[7]  
EMTAGE PC, 2002, J INTERFERON CYTOKIN, V5, P573
[8]   Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells (Reprinted from vol 4, pg 330-336, 2003) [J].
Fontenot, Jason D. ;
Gavin, Marc A. ;
Rudensky, Alexander Y. .
JOURNAL OF IMMUNOLOGY, 2017, 198 (03) :986-992
[9]   Defective suppression of Th2 cytokines by CD4+CD25+ regulatory T cells in birch allergics during birch pollen season [J].
Grindebacke, H ;
Wing, K ;
Andersson, AC ;
Suri-Payer, E ;
Rak, S ;
Rudin, A .
CLINICAL AND EXPERIMENTAL ALLERGY, 2004, 34 (09) :1364-1372
[10]   Human T regulatory cells can use the perforin pathway to cause autologous target cell death [J].
Grossman, WJ ;
Verbsky, JW ;
Barchet, W ;
Colonna, M ;
Atkinson, JP ;
Ley, TJ .
IMMUNITY, 2004, 21 (04) :589-601