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

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

Stable Identifier

R-HSA-8877330

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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

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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
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
10837065	Regulatory T cells in autoimmmunity* Shevach, EM	Annu. Rev. Immunol.	2000
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
15032588	Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses Sakaguchi, S	Annu. Rev. Immunol.	2004
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
11526392	Regulatory T cells in the control of immune pathology Maloy, KJ, Powrie, F	Nat. Immunol.	2001
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
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