Person:
Sefik, Esen

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Sefik

First Name

Esen

Name

Sefik, Esen

Filters

20152

Settings

Author's Publications: search.filters.isAuthorOfPublication.ef8fface-f734-4e6a-a019-c791e6bb8a8e

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling
    (2015) Charbonnier, Louis-Marie; Wang, Sen; Georgiev, Peter; Sefik, Esen; Chatila, Talal
    Notch receptors direct the differentiation of T helper (TH) cell subsets, but their influence on regulatory T (Treg) cell responses is obscure. We here report that lineage-specific deletion of components of the Notch pathway enhanced Treg cell-mediated suppression of TH1 responses, and protected against their TH1 skewing and apoptosis. Expression in Treg cells of gain of function transgene encoding Notch1 intracellular domain resulted in lymphoproliferation, exacerbated TH1 responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired Treg cell fitness, promoted the acquisition by Treg cells of a TH1 cell-like phenotype, whereas Rictor-dependent non-canonical Notch signaling activated the AKT-Foxo1 axis and impaired Foxp3 epigenetic stability. These findings establish a critical role for Notch signaling in controlling peripheral Treg cell functions.
  • No Thumbnail Available
    Publication
    Individual Microbes Shape Various Parts of the Immune System
    (2015-09-22) Sefik, Esen; Carroll, Michael; Chatila, Talal; An, Dingding; Ivanov, Ivaylo
    The gastrointestinal tract, home to a vast number of bacteria, requires finely-tuned regulatory and effector immune mechanisms to maintain homeostasis and tolerance. In a large-scale screen, we studied the impacts of single microbes on major immune populations, whole intestinal tissue homeostasis and metabolism. Bacteria interacted with the host at multiple levels including cytokine responses, accumulation of various T cells, alterations in composition of mononuclear phagocytes and induction of epithelial cell genes as measured by transcriptome analysis of whole intestinal tissue. Interestingly, taxonomically unrelated bacteria elicited similar immune phenotypes and metabolic effects. A more focused analysis of the induction of regulatory mechanisms revealed a microbiota-dependent, context-specific transcriptional control of Foxp3+ regulatory T cells and of IL17 producing T cells. These facets were both regulated by Rorγ, a transcription factor known for its antagonistic effects on Foxp3. Paradoxically, Rorγ expression induced by bacteria in colonic Foxp3+ regulatory T cells was necessary for function of these cells especially in the context of IL17 and IFNγ-mediated colitis. Overall, this large-scale screen provides a comprehensive study of how individual bacterial species shape many aspects of the host immunity and metabolism, and exemplifies a microbiota-dependent, context-specific mechanism that potentiates function in Foxp3+ regulatory T cells.