TY - JOUR
T1 - Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo
AU - Felices, Martin
AU - Yin, Catherine C.
AU - Kosaka, Yoko
AU - Kang, Joonsoo
AU - Berg, Leslie J.
PY - 2009/5/19
Y1 - 2009/5/19
N2 - In conventional αβ T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates αβ T cell development lineage commitment, and effector function. A well established feature of Itk -/- mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is γδ T cells, as normal IgE levels are observed in Itk -/-Tcrd -/- mice. When stimulated through the γδ TCR, Itk -/- γδT cells produce high levels of Th2 cytokines, but diminished IFNγ. in addition, activated Itk -/- γδT cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that γδ T cells numbers are increased in ltk -/- mice, most notably the Vy1.1 +V86.3 + subset that represents the dominant population of γδ NKT cells, Iltk -/- γδ NKT cells also have increased expression of PLZF, a transcription factor required for αβ NKT cells, indicating a common molecular program between αβ and γδ NKT cell lineages. Together, these data indicate that Itk signaling regulates γδ T cell lineage development and effector function and is required to control IgE production in vivo.
AB - In conventional αβ T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates αβ T cell development lineage commitment, and effector function. A well established feature of Itk -/- mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is γδ T cells, as normal IgE levels are observed in Itk -/-Tcrd -/- mice. When stimulated through the γδ TCR, Itk -/- γδT cells produce high levels of Th2 cytokines, but diminished IFNγ. in addition, activated Itk -/- γδT cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that γδ T cells numbers are increased in ltk -/- mice, most notably the Vy1.1 +V86.3 + subset that represents the dominant population of γδ NKT cells, Iltk -/- γδ NKT cells also have increased expression of PLZF, a transcription factor required for αβ NKT cells, indicating a common molecular program between αβ and γδ NKT cell lineages. Together, these data indicate that Itk signaling regulates γδ T cell lineage development and effector function and is required to control IgE production in vivo.
KW - T cell development
KW - T cell differentiation
KW - T cell signaling
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UR - http://www.scopus.com/inward/citedby.url?scp=66249138887&partnerID=8YFLogxK
U2 - 10.1073/pnas.0808459106
DO - 10.1073/pnas.0808459106
M3 - Article
C2 - 19416854
AN - SCOPUS:66249138887
SN - 0027-8424
VL - 106
SP - 8308
EP - 8313
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -