RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)

Stable Identifier
R-HSA-8877330
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

The complex of CBFB and RUNX1 (AML1) controls transcription of the FOXP3 gene. FOXP3 is a transcription factor that acts as a key regulator of development and function of regulatory T lymphocytes (Tregs). Tregs are CD25+CD4+ T lymphocytes involved in suppression of aberrant immune responses seen in autoimmune diseases and allergies. FOXP3 can bind to RUNX1 and control transcriptional activity of the RUNX1:CBFB complex. RUNX1 stimulates transcription of IL2 and IFNG1 (IFN-gamma), and the expression of these two genes is repressed upon binding of FOXP3 to RUNX1. The complex of FOXP3 and RUNX1, on the other hand, stimulates transcription of cell surface markers of Tregs, such as CD25, CTLA-4 and GITR. In the absence of FOXP3, RUNX1 represses transcription of these genes (Shevach 2000, Maloy and Powrie 2001, Sakaguchi 2004, Ono et al. 2007, Kitoh et al. 2009).
The RUNX1:CBFB complex directly stimulates transcription of the CR1 gene, encoding Complement receptor type 1 (CD35) (Kim et al. 1999, Rho et al. 2002). Expression of CR1 on the surface of activated T cells contributes to generation of Tregs (Torok et al. 2015).

Literature References
PubMed ID Title Journal Year
16873067 FOXP3 controls regulatory T cell function through cooperation with NFAT

Wu, Y, Borde, M, Heissmeyer, V, Feuerer, M, Lapan, AD, Stroud, JC, Bates, DL, Guo, L, Han, A, Ziegler, SF, Mathis, D, Benoist, C, Chen, L, Rao, A

Cell 2006
10533284 AML1, the target of chromosomal rearrangements in human leukemia, regulates the expression of human complement receptor type 1 (CR1) gene

Kim, JH, Lee, S, Rho, JK, Choe, SY

Int. J. Biochem. Cell Biol. 1999
25742728 Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells

Török, K, Dezső, B, Bencsik, A, Uzonyi, B, Erdei, A

Immunol. Lett. 2015
11526392 Regulatory T cells in the control of immune pathology

Maloy, KJ, Powrie, F

Nat. Immunol. 2001
19800266 Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells

Kitoh, A, Ono, M, Naoe, Y, Ohkura, N, Yamaguchi, T, Yaguchi, H, Kitabayashi, I, Tsukada, T, Nomura, T, Miyachi, Y, Taniuchi, I, Sakaguchi, S

Immunity 2009
15032588 Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses

Sakaguchi, S

Annu. Rev. Immunol. 2004
12220513 Correlation between cellular localization of TEL/AML1 fusion protein and repression of AML1-mediated transactivation of CR1 gene

Rho, JK, Kim, JH, Yu, J, Choe, SY

Biochem. Biophys. Res. Commun. 2002
10837065 Regulatory T cells in autoimmmunity*

Shevach, EM

Annu. Rev. Immunol. 2000
17377532 Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1

Ono, M, Yaguchi, H, Ohkura, N, Kitabayashi, I, Nagamura, Y, Nomura, T, Miyachi, Y, Tsukada, T, Sakaguchi, S

Nature 2007
Participants
Participant Of
Event Information
Orthologous Events
Authored
Reviewed
Created