Unexpected Role for the B Cell-Specific Src Family Kinase B Lymphoid Kinase in the Development of IL-17-Producing γδ T Cells

被引:78
作者
Laird, Renee M. [1 ]
Laky, Karen [2 ]
Hayes, Sandra M. [1 ]
机构
[1] SUNY Syracuse, Dept Microbiol & Immunol, Upstate Med Univ, Syracuse, NY 13210 USA
[2] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
PROTEIN-TYROSINE KINASES; ALPHA-BETA; INTERFERON-GAMMA; LISTERIA-MONOCYTOGENES; INTERLEUKIN-7; RECEPTOR; TCR SIGNALS; IFN-GAMMA; EXPRESSION; DIFFERENTIATION; COMMITMENT;
D O I
10.4049/jimmunol.1002766
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The Ag receptors on alpha beta and gamma delta T cells differ not only in the nature of the ligands that they recognize but also in their signaling potential. We hypothesized that the differences in alpha beta- and gamma delta TCR signal transduction were due to differences in the intracellular signaling pathways coupled to these two TCRs. To investigate this, we used transcriptional profiling to identify genes encoding signaling molecules that are differentially expressed in mature alpha beta and gamma delta T cell populations. Unexpectedly, we found that B lymphoid kinase (Blk), a Src family kinase expressed primarily in B cells, is expressed in gamma delta T cells but not in alpha beta T cells. Analysis of Blk-deficient mice revealed that Blk is required for the development of IL-17-producing gamma delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. The Journal of Immunology, 2010, 185: 6518-6527.
引用
收藏
页码:6518 / 6527
页数:10
相关论文
共 55 条
[1]   Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development [J].
Agosti, V ;
Corbacioglu, S ;
Ehlers, I ;
Waskow, C ;
Sommer, G ;
Berrozpe, G ;
Kissel, H ;
Tucker, CM ;
Manova, K ;
Moore, MAS ;
Rodewald, HR ;
Besmer, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (06) :867-878
[2]   Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells [J].
Awasthi, Amit ;
Riol-Blanco, Lorena ;
Jaeger, Anneli ;
Korn, Thomas ;
Pot, Caroline ;
Galileos, George ;
Bettelli, Estelle ;
Kuchroo, Vijay K. ;
Oukka, Mohamed .
JOURNAL OF IMMUNOLOGY, 2009, 182 (10) :5904-5908
[3]   CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity [J].
Azzam, HS ;
Grinberg, A ;
Lui, K ;
Shen, H ;
Shores, EW ;
Love, PE .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (12) :2301-2311
[4]   ANTIIMMUNOGLOBULIN STIMULATION OF LYMPHOCYTES-B ACTIVATES SRC-RELATED PROTEIN-TYROSINE KINASES [J].
BURKHARDT, AL ;
BRUNSWICK, M ;
BOLEN, JB ;
MOND, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (16) :7410-7414
[5]   γδ T cells:: Functional plasticity and heterogeneity [J].
Carding, SR ;
Egan, PJ .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (05) :336-345
[6]   Protection of the intestinal mucosa by intraepithelial γδ T cells [J].
Chen, YP ;
Chou, K ;
Fuchs, E ;
Havran, WL ;
Boismenu, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) :14338-14343
[7]   Recognition by gamma/delta T cells [J].
Chien, YH ;
Jores, R ;
Crowley, MP .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :511-532
[8]   Stage-specific and differential notch dependency at the αβ and γδ T lineage bifurcation [J].
Ciofani, Maria ;
Knowles, Gisele C. ;
Wiest, David L. ;
von Boehmer, Harald ;
Zuniga-Pflucker, Juan Carlos .
IMMUNITY, 2006, 25 (01) :105-116
[9]   The complexity of signaling pathways activated by the BCR [J].
DeFranco, AL .
CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (03) :296-308
[10]   SPECIFIC EXPRESSION OF A TYROSINE KINASE GENE, BLK, IN B-LYMPHOID CELLS [J].
DYMECKI, SM ;
NIEDERHUBER, JE ;
DESIDERIO, SV .
SCIENCE, 1990, 247 (4940) :332-336