NOMIS Researcher(s)
Published in Immunity
Regulation of Foxp3 expression is central to Treg cell development and function. Loo et al. performed a genome-wide CRISPR screen and identified the Brd9-containing ncBAF complex as a key regulator of Foxp3 and a subset of its target genes, which could be targeted to cripple Treg cell function and improve anti-tumor immunity.
Research field(s)
Health Sciences, Clinical Medicine, Immunology
NOMIS Researcher(s)
Published in Current Opinion in Immunology
Two distinct defense strategies provide a host with survival to infectious diseases: resistance and tolerance. Resistance is dependent on the ability of the host to kill pathogens. Tolerance promotes host health while having a neutral to positive impact of pathogen fitness. Immune responses are almost inevitably defined in terms of pathogen resistance. Recent evidence has shown, however, that several effects attributed to activation of innate and adaptive immune mechanisms, cannot be readily explained with the paradigm of immunity as effectors of microbial destruction. This review focuses on integrating the concept of disease tolerance into recent studies of immune system function related to the regulation and resolution of tissue damage, T cell exhaustion, and tolerance to innocuous antigen.
Research field(s)
Health Sciences, Clinical Medicine, Immunology
NOMIS Researcher(s)
Published in Trends in Immunology
T regulatory (Treg) cells are central to the maintenance of immune homeostasis. The transcription factor forkhead box P3 (Foxp3) is essential for specifying the Treg cell lineage during development, and continued expression of Foxp3 in mature Treg cells is necessary for suppressive function. Loss of Foxp3 expression in Treg cells is associated with autoimmune pathology. Here, we review recent insights into the mechanisms that maintain Treg cell stability and function, and place these findings within the broader understanding of mechanisms that establish Treg cell identity during development. We integrate emerging principles in Treg cell lineage maintenance with the mechanisms that allow Treg cells to sense and respond to varied inflammatory environments, and outline important areas of future inquiry in this context.
Research field(s)
Health Sciences, Clinical Medicine, Immunology
NOMIS Researcher(s)
Published in Cell
The homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear whether mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation. © 2014 Elsevier Inc.
Research field(s)
Health Sciences, Biomedical Research, Developmental Biology
