Defining Transcriptional Signatures of Human Hair Follicle Cell States.

The epidermis and its appendage, the hair follicle, represent an elegant developmental system in which cells are replenished with regularity because of controlled proliferation, lineage specification, and terminal differentiation. Although transcriptome data exists for human epidermal and dermal cells, the hair follicle remains poorly characterized. Through single-cell resolution profiling of the epidermis and anagen hair follicle, we characterized the anatomical, transcriptional, functional, and pathological profiles of distinct epidermal, hair follicle, and hair follicle-associated cell subpopulations including melanocytes, endothelial cells, and immune cells.

IL-1β Induces the Rapid Secretion of the Antimicrobial Protein IL-26 from Th17 Cells.

Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1β dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with as compared with 48 hours for IFN-γ and IL-17A.

Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria.

Human CD8 cytotoxic T lymphocytes (CTLs) contribute to antimicrobial defense against intracellular pathogens through secretion of cytotoxic granule proteins granzyme B, perforin, and granulysin. However, CTLs are heterogeneous in the expression of these proteins, and the subset(s) responsible for antimicrobial activity is unclear. Studying human leprosy, we found that the subset of CTLs coexpressing all three cytotoxic molecules is increased in the resistant form of the disease, can be expanded by interleukin-15 (IL-15), and is differentiated from naïve CD8 T cells by Langerhans cells.

The mutable vaccine for mutable viruses.

Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies.

C3d regulates immune checkpoint blockade and enhances antitumor immunity.

Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. What orchestrates these controls is unknown. We report that free C3d, a fragment of the third component of complement, inside tumor cells - or associated with irradiated tumor cells and unattached to antigen - recruits, accelerates, and amplifies antitumor T cell responses, allowing immunity to reverse or even to prevent tumor growth.

Calcinosis cutis occurring in association with autoimmune connective tissue disease: the Mayo Clinic experience with 78 patients, 1996-2009.

Objective: To describe characteristics and treatment of patients with calcinosis cutis in the clinical setting of autoimmune connective tissue disease (ACTD).

Design: Retrospective study.

Setting: Tertiary referral center.

Myelodysplastic syndrome presenting as generalized granulomatous dermatitis.

Background: Granulomatous dermatitis has rarely been reported as a manifestation of leukemia or myelodysplastic syndrome (MDS). We describe a case of widespread granulomatous dermatitis that preceded the diagnosis of MDS by 2 years.

Observations: A 71-year-old man developed a generalized, mildly pruritic eruption that slowly progressed over a 2-year period.

The rate of mutation of a single gene.

The rate of mutation refers to the probability that a unit length of DNA (generally a base pair) mutates with time. Fluctuation analysis or mutant accumulation assays applied to phenotypic changes measure mutation rates of cells. However, only a few phenotypic changes indicative of mutations are known thus limiting the analysis to those rare genes.

Noncognate function of B cells in transplantation.

How B cells affect the outcome of transplants is a question of enduring interest. Initial efforts to answer that question suggested, wrongly, that B cells have no impact on transplantation. Now, however, B cells are known to influence not only the outcome of vascularized grafts through the production of anti-donor antibodies but also the competence of cellular immunity through a number of physiologic functions.

New insights into the functions of B cells.

Organ transplants between genetically different individuals elicit powerful immune responses that invariably cause rejection in the absence of immune suppression. Among the immune responses elicited by organ allografts, B-cell responses causing antibody-mediated rejection are one of the most vexing. However, recent advances in the field indicate that B cells and antibodies' contribution to immunity extends well beyond the traditional functions ascribed to antibodies.

HIV genes diversify in B cells.

Mutation of the human immunodeficiency virus by host cells inhibits viral dissemination by creating non-functional variants. However, viral mutation does not always eliminate the ability of the virus to disseminate and, in fact, is thought to promote persistence by generating functional mutants that evade immunity or drugs. How and where HIV mutates is not known.

Transplantation tolerance in NF-kappaB-impaired mice is not due to regulation but is prevented by transgenic expression of Bcl-xL.

NF-kappaB is a key regulator of transcription after TCR and costimulatory receptor ligation. To determine the role of T cell-intrinsic NF-kappaB activation in acute allograft rejection, we used IkappaBalphaDeltaN-Tg mice (H-2b) that express an inhibitor of NF-kappaB restricted to the T cell compartment. We have previously shown that these mice permanently accept fully allogeneic (H-2d) cardiac grafts and secondary donor skin grafts, and that splenocytes from these tolerant mice have reduced alloreactivity when restimulated in vitro.

Loss of EPC-1/PEDF expression during skin aging in vivo.

EPC-1/PEDF (early population doubling level cDNA-1/retinal pigmented epithelium-derived factor) is a single-copy, quiescence-specific gene that is transcribed into a 1.5 kb mRNA and then translated into a 50 kDa secreted protein that is a potent inhibitor of angiogenesis. EPC-1 expression has been detected in a number of cultured cell lines, including lung and skin fibroblasts, retinal pigmented epithelial cells, and endometrial stromal fibroblasts.