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

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 were not known to be simultaneously generated and coexist.

JunB Controls Intestinal Effector Programs in Regulatory T Cells.

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 controlling tissue-specific gene expression in Tregs remain unclear. Here, we find that the AP-1 transcription factor JunB regulates the intestinal adaptation of Tregs by controlling select gene expression programs in multiple Treg subsets.

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

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 literature vary widely in efficiency and complexity, limiting their comparison across studies. Here, we present a standardized and robust method for the isolation and in vitro differentiation of six CD4 T cell subsets from mouse naïve T cells.

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

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 undefined. Here, we identified c-Maf as an essential regulator of ILC3 homeostasis and plasticity that limits physiological ILC1 conversion.

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

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 complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops.

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

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 Publisher Correction.

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

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 essential to all Tγδ17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance.

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

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 organismal homeostasis. However, despite extensive functional characterization, the factors driving Treg specialization are largely unknown.

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

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 identity. JunB activates expression of Th17 lineage-specifying genes and coordinately represses genes controlling Th1 and regulatory T-cell fate.