Maria Ciofani

Journal article J Exp Med · January 6, 2020 Featured Publication CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefin ... Full text Link to item Cite

In Vitro Differentiation of CD4+ T Cell Effector and Regulatory Subsets.

Journal article Methods Mol Biol · 2020 Featured Publication In vitro differentiation of naïve CD4+ T cells into effector and regulatory subsets offers a means to acquire large numbers of relatively homogeneous cell populations for experimentation. However, culture systems for T cell differentiation described in the ... Full text Link to item Cite

Regulation of γδ T Cell Effector Diversification in the Thymus.

Journal article Front Immunol · 2020 Featured Publication γδ T cells are the first T cell lineage to develop in the thymus and take up residence in a wide variety of tissues where they can provide fast, innate-like sources of effector cytokines for barrier defense. In contrast to conventional αβ T cells that egre ... Full text Link to item Cite

JunB Controls Intestinal Effector Programs in Regulatory T Cells.

Journal article Front Immunol · 2020 Featured Publication Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors ... Full text Link to item Cite

Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.

Journal article Nat Commun · September 19, 2019 Featured Publication Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits c ... Full text Open Access Link to item Cite

Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.

Journal article Genome Res · March 2019 Featured Publication Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The assay for transposase-accessible chromatin (ATAC)-seq, coupled with TF motif analys ... Full text Link to item Cite

The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.

Journal article Nat Immunol · January 2019 Featured Publication γδ T cells that produce the cytokine IL-17 (Tγδ17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tγδ17 specialization restricted to various Vγ subsets are known, a commitment factor essenti ... Full text Link to item Cite

JunB controls intestinal effector programs in regulatory T cells

Journal article · 2019 Featured Publication Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors ... Full text Cite

Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes.

Journal article J Immunol · December 15, 2017 Featured Publication Regulatory T cells (Tregs) adopt specialized phenotypes defined by coexpression of lineage-defining transcription factors, such as RORγt, Bcl-6, or PPARγ, alongside Foxp3. These Treg subsets have unique tissue distributions and diverse roles in maintaining ... Full text Link to item Cite

JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation.

Journal article Nat Commun · August 21, 2017 Featured Publication T helper 17 (Th17) cell plasticity contributes to both immunity and autoimmunity; however, the factors that control lineage flexibility are mostly unknown. Here we show the activator protein-1 (AP-1) factor JunB is an essential regulator of Th17 cell ident ... Full text Open Access Link to item Cite

A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.

Journal article Science · November 16, 2012 Featured Publication Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given t ... Full text Link to item Cite

A validated regulatory network for Th17 cell specification.

Journal article Cell · October 12, 2012 Featured Publication Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other essential transcription factors (TFs). We have used an itera ... Full text Link to item Cite

Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.

Journal article Nature · April 28, 2011 Featured Publication CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans ... Full text Link to item Cite

Determining γδ versus αß T cell development.

Journal article Nat Rev Immunol · September 2010 Featured Publication The thymus produces several types of functionally distinct T cell subsets. However, at a more fundamental level only two genetically distinct T cell lineages exist: the γδ and αß T cell lineages. Precisely how these two T cell lineages are generated from c ... Full text Link to item Cite

Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells.

Journal article Genes Dev · April 1, 2010 Featured Publication The stability of a lineage program (cellular memory) is dependent on mechanisms that epigenetically maintain active or repressed states of gene expression (transcriptional memory). Although epigenetic silencing of genes has been clearly demonstrated from y ... Full text Link to item Cite

Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.

Journal article Nat Med · October 2007 Featured Publication Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias and lymphomas (T-ALL), making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation ... Full text Link to item Cite

Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.

Journal article Immunity · July 2006 Featured Publication Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of alphabeta T lineage cells. However, the role of Notch signals during alphabeta versus gammadelta T lineage decision remains controversial. Here, we addr ... Full text Link to item Cite

Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.

Journal article Nat Immunol · September 2005 Featured Publication Notch signals are necessary for the functional outcomes of T cell receptor beta-selection, including differentiation, proliferation and rescue from apoptosis. The mechanism underlying this requirement for T cell development is unknown. Here we show that No ... Full text Link to item Cite

Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.

Journal article J Immunol · May 1, 2004 Featured Publication The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch re ... Full text Link to item Cite