TGF-β converts apoptotic stimuli into the signal for Th9 differentiation.

نویسندگان

  • Mariko Takami
  • Robert B Love
  • Makio Iwashima
چکیده

Naturally arising CD4(+)CD25(+)FoxP3(+) regulatory T cells (nTregs) have an essential role in maintenance of immune homeostasis and peripheral tolerance. Previously, we reported that conventional CD4(+) and CD8(+) T cells undergo p53-induced CD28-dependent apoptosis (PICA) when stimulated with a combination of immobilized anti-CD3 and anti-CD28 Abs, whereas nTregs expand robustly under the same conditions, suggesting that there is a differential survival mechanism against PICA between conventional T cells and nTregs. In this study, we demonstrate that TGF-β signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-β is present, conventional T cells become resistant to PICA and undergo robust expansion instead of apoptosis, with reduction of the proapoptotic protein Bim and FoxO3a. A substantial fraction of PICA-resistant T cells expressed IL-9 (T(H)9 cells). Moreover, the presence of IL-6 along with TGF-β led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-β in the homeostasis of regulatory T cells and effector T cell differentiation and expansion.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Regulatory T cells vs Th17: differentiation of Th17 versus Treg, are the mutually exclusive?

Naive CD4(+) cells differentiate into T helper (Th1, Th2, Th9, Th17) and regulatory T (Treg) cells to execute their immunologic function. Whereas TGF-β suppresses Th1 and Th2 cell differentiation, this cytokine promotes Th9, Th17 and Foxp3(+) regulatory T cells depending upon the presence of other cytokines. IL-6 promotes Th17, but suppresses regulatory T cell differentiation. Moreover, natural...

متن کامل

TGF-β1 enhanced myocardial differentiation through inhibition of the Wnt/β-catenin pathway with rat BMSCs

Objective(s): To investigate and test the hypotheses that TGF-β1 enhanced myocardial differentiation through Wnt/β-catenin pathway with rat bone marrow mesenchymal stem cells (BMSCs).Materials and Methods: Lentiviral vectors carrying the TGF-β1 gene were transduced into rat BMSCs firstly. Then several kinds of experimental methods were u...

متن کامل

The role of T helper 9(Th9) against Infectious Diseases

Background and aims: Infectious diseases are disorders caused by organisms such as bacteria, viruses, fungi or parasites .The Th9 subset develops in response to combined signals from TGF-b and IL-4 among a cacophony of other cytokines in an extracellular milieu. T helper 9 (Th9) cells,  as a novel CD4 T cell subset, seem to play a complex role in the outcome of specific immune responses. In thi...

متن کامل

STAT6-dependent regulation of Th9 development.

Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration of signals that may promote the development of opposing pathways. A recent example of this paradigm is the IL-9-secreting Th9 cell that develops in response to TGF-β and IL-4, cytokines that, in isolation, promote the development of i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 188 9  شماره 

صفحات  -

تاریخ انتشار 2012