Scholars@Duke
Maria Ciofani

Maria Ciofani

Associate Professor of Integrative Immunobiology
Integrative Immunobiology
maria.ciofani@duke.edu
128 Jones Bldg, 207 Researchr, 3010 DUMC, Durham, NC 27710

Selected Publications

E proteins control the development of NKγδT cells through their invariant T cell receptor.

Journal Article Nat Commun · June 13, 2024 T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T ce ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans.

Journal Article mBio · October 31, 2023 Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human ... Full text Link to item Cite

Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Journal Article Sci Immunol · October 20, 2023 Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including TH17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in t ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22 modified FK520 analog against C. neoformans.

Journal Article bioRxiv · July 11, 2023 UNLABELLED: Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the ... Full text Link to item Cite

Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit In Vivo Therapeutic Efficacy against Cryptococcus.

Journal Article mBio · June 28, 2022 Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine ... Full text Open Access Link to item Cite

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Journal Article Nat Methods · August 2021 CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both culture ... Full text Link to item Cite

Functional heterogeneity of alveolar macrophage population based on expression of CXCL2.

Journal Article Sci Immunol · August 7, 2020 Alveolar macrophages (AMs) are the major lung-resident macrophages and have contradictory functions. AMs maintain tolerance and tissue homeostasis, but they also initiate strong inflammatory responses. However, such opposing roles within the AM population ... Full text Link to item Cite

Tγδ17 cells build up the nerve.

Journal Article Nat Immunol · April 2020 Full text Link to item Cite

c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.

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

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

Journal Article Nat Immunol · May 2019 In the version of this article initially published, the top right plot in Figure 4a was aligned incorrectly. The error has been corrected in the HTML and PDF versions of the article. The original and corrected figures are provided in the accompanying Publi ... Full text 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

Comparative and functional evaluation of in vitro generated to ex vivo CD8 T cells.

Journal Article J Immunol · October 1, 2012 The generation of the cytotoxic CD8 T cell response is dependent on the functional outcomes imposed by the intrathymic constraints of differentiation and self-tolerance. Although thymic function can be partly replicated in vitro using OP9-DL1 cell cultures ... Full text Link to item Cite

Dynamic microRNA gene transcription and processing during T cell development.

Journal Article J Immunol · April 1, 2012 By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, and in a dy ... 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

Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.

Journal Article Immunity · October 16, 2009 alphabeta and gammadelta T cells arise from a common thymocyte progenitor during development in the thymus. Emerging evidence suggests that the pre-T cell receptor (pre-TCR) and gammadelta T cell receptor (gammadeltaTCR) play instructional roles in specify ... Full text Link to item Cite

Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.

Journal Article J Immunol · October 1, 2007 Development of immature T cell precursors beyond the beta-selection checkpoint is regulated by signals transduced by the pre-TCR complex. The pre-TCR-induced differentiation program is orchestrated by a network of transcription factors that serve to integr ... 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

The thymus as an inductive site for T lymphopoiesis.

Journal Article Annu Rev Cell Dev Biol · 2007 Like all hematopoietic cells, T lymphocytes are derived from bone-marrow-resident stem cells. However, whereas most blood lineages are generated within the marrow, the majority of T cell development occurs in a specialized organ, the thymus. This distincti ... 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

Pre-T cell receptor's clashing signals: "should I stay or should I go".

Journal Article Immunity · June 2006 In this issue of Immunity, Kersh and colleagues (Xi et al., 2006) investigate the regulatory network that permits two otherwise clashing cellular processes--proliferation and gene rearrangement--to occur at temporally distinct periods following the formati ... Full text Link to item Cite

A survival guide to early T cell development.

Journal Article Immunol Res · 2006 The survival of immature T cell precursors is dependent on both thymus-derived extrinsic signals and self-autonomous pre-TCR-mediated signals. While the role of cytokines and the pre-TCR in promoting thymocyte survival has been well established, the relati ... 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

Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.

Journal Article J Exp Med · August 16, 2004 Notch signaling has been shown to play a pivotal role in inducing T lineage commitment. However, T cell progenitors are known to retain other lineage potential long after the first point at which Notch signaling is required. Thus, additional requirements f ... 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