Document Type

Article

Publication Date

2020

Publication Title

Cell Reports

Volume

33

Issue

1

Pages

24 pp.

DOI

10.1016/j.celrep.2020.108219

Abstract

Bone morphogenic proteins (BMPs) are members of the transforming growth factor β (TGF-β) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1α (BMPR1α) sustains expression of FOXP3 in Treg cells in peripheral lymphoid tissues. BMPR1α signaling promotes molecular circuits supporting acquisition and preservation of Treg cell phenotype and inhibiting differentiation of pro-inflammatory effector Th1/Th17 CD4+ T cell. Mechanistically, increased expression of KDM6B (JMJD3) histone demethylase, an antagonist of the polycomb repressive complex 2, underlies lineage-specific changes of T cell phenotypes associated with abrogation of BMPR1α signaling. These results reveal that BMPs are immunoregulatory cytokines mediating maturation and stability of peripheral FOXP3+ regulatory T cells (Treg cells) and controlling generation of iTreg cells. Thus, we establish that BMPs, a large cytokine family, are an essential link between stromal tissues and the adaptive immune system involved in sustaining tissue homeostasis by promoting immunological tolerance.

Comments

This is an open access article under the Attribution-NonCommercial-NoDerivatives 4.0 International License.

Original Publication Citation

Browning, L. M., Miller, C., Kuczma, M., Pietrzak, M., Jing, Y., Rempala, G., Muranski, P., Ignatowicz, L., & Kraj, P. (2020). Bone morphogenic proteins are immunoregulatory cytokines controlling FOXP3+ Treg Cells. Cell reports, 33(1), 24 pp., Article 108219. https://doi.org/10.1016/j.celrep.2020.108219

ORCID

0000-0003-2231-5487 (Browning), 0000-0003-2917-017X (Miller)

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