The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Primary Apocrine Adenocarcinoma of the Axilla

Primary apocrine adenocarcinoma (AA) is a rare malignant cutaneous neoplasm that typically arises in areas of high apocrine gland density such as the axillae and the anogenital region. Due to the nonspecific clinical manifestation of AA, the differential diagnosis may be broad. The rarity of this neoplasm has led to a relative lack of well-established histologic and immunohistochemical diagnostic criteria, further complicating the diagnosis of AA. We report the case of a 49-year-old man with primary AA of the left axilla and provide a review of the clinical and histologic findings, epidemiology, and treatment modalities of this rare cutaneous neoplasm

T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype

IL-23, an IL-12-related cytokine, induces an IL-17-secreting T-helper phenotype that is involved in autoimmune diseases and host defense against certain pathogens. Although the transcription factors required for development of IL-23-stimulated cells are unknown, we show that T-bet is a critical negative regulator of the IL-23-primed T-cell phenotype, which we term Th1β. Th1 or Th1β Tbx21-/- cultures secrete higher than WT levels of IL-17 in response to T-cell receptor (TCR) or IL-23 + IL-18 stimulation. Ectopic T-bet expression in Th1β cells promotes IFN-γ secretion but decreases IL-17 production. Although antigen-receptor stimulation of Th1β cells stimulates IL-17 production, it also induces the IFN-γ-independent expression of T-bet and progression to a Th1 cytokine secretion pattern. T-bet is required for the progression to the Th1 phenotype, because Tbx21-/- Th1β cultures maintain the IL-17-secreting phenotype after 2 weeks of culture. Addition of IFN-γ to Tbx21-/- Th1β cultures cannot recover the progression to the Th1 phenotype, suggesting T-bet, rather than IFN-γ, mediates Th1β to Th1 progression. The transient nature of the Th1β phenotype suggests that these cells are a component of type I immunity and that T-bet expression is a critical determinant of Th1 versus Th1β cell fate

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair.

Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair-follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a SC fate-mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal-barrier repair after injury. Depletion of Treg cells impaired skin-barrier regeneration and was associated with a Th17 inflammatory response and failed HFSC differentiation. In this setting, damaged epithelial cells preferentially expressed the neutrophil chemoattractant CXCL5, and blockade of CXCL5 or neutrophil depletion restored barrier function and SC differentiation after epidermal injury. Thus, Treg-cell regulation of localized inflammation enables HFSC differentiation and, thereby, skin-barrier regeneration, with implications for the maintenance and repair of other barrier tissues

Regulatory T cells in skin are uniquely poised to suppress profibrotic immune responses

At the center of fibrosing diseases is the aberrant activation of tissue fibroblasts. The cellular and molecular mechanisms of how the immune system augments fibroblast activation have been described; however, little is known about how the immune system controls fibroblast function in tissues. Here, we identify regulatory T cells (Tregs) as important regulators of fibroblast activation in skin. Bulk cell and single-cell analysis of Tregs in murine skin and lungs revealed that Tregs in skin are transcriptionally distinct and skewed toward T helper 2 (TH2) differentiation. When compared with Tregs in lung, skin Tregs preferentially expressed high levels of GATA3, the master TH2 transcription factor. Genes regulated by GATA3 were highly enriched in skin "TH2 Treg" subsets. In functional experiments, Treg depletion resulted in a preferential increase in TH2 cytokine production in skin. Both acute depletion and chronic reduction of Tregs resulted in spontaneous skin fibroblast activation, profibrotic gene expression, and dermal fibrosis, all of which were exacerbated in a bleomycin-induced murine model of skin sclerosis. Lineage-specific deletion of Gata3 in Tregs resulted in an exacerbation of TH2 cytokine secretion that was preferential to skin, resulting in enhanced fibroblast activation and dermal fibrosis. Together, we demonstrate that Tregs play a critical role in regulating fibroblast activation in skin and do so by expressing a unique tissue-restricted transcriptional program that is mediated, at least in part, by GATA3

Constitutively active STAT6 predisposes toward a lymphoproliferative disorder

Signal transducer and activator of transcription 6 (STAT6) is critical for IL-4 and IL-13 responses, and necessary for the normal development of Th2 cells. We previously generated mice that express a constitutively active STAT6 (STAT6VT) under control of the CD2 locus control region, which directs expression to the T-cell compartment. We now describe that a small proportion of these mice (∼5%) develop a spontaneous lymphoproliferative disease (LPD) that results in dramatic splenomegaly. The cell populations observed in the LPD spleens can be divided into 2 categories, those that are composed of mixed lineage cells and those that are predominantly T cells with a phenotype similar to that in autoimmune lymphoproliferative syndrome (ALPS) patients. These data suggest that while active STAT6 is not a transforming factor, expression in T cells predisposes toward the development of lymphoproliferative disorders

Layilin augments integrin activation to promote antitumor immunity.

Tumor-infiltrating CD8+ T cells mediate antitumor immune responses. However, the mechanisms by which T cells remain poised to kill cancer cells despite expressing high levels of inhibitory receptors are unknown. Here, we report that layilin, a C-type lectin domain-containing membrane glycoprotein, is selectively expressed on highly activated, clonally expanded, but phenotypically exhausted CD8+ T cells in human melanoma. Lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Congruently, gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. On a molecular level, layilin colocalized with integrin αLβ2 (LFA-1) on T cells, and cross-linking layilin promoted the activated state of this integrin. Accordingly, LAYN deletion resulted in attenuated LFA-1-dependent cellular adhesion. Collectively, our results identify layilin as part of a molecular pathway in which exhausted or "dysfunctional" CD8+ T cells enhance cellular adhesiveness to maintain their cytotoxic potential