SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators.

The identity and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. Recently single-cell technologies have been developed that enable simultaneous quantitative analysis of cell-surface receptor expression with transcriptional states. To date, these datasets have not been used to systematically develop cell-context-specific maps of the interface between signaling and transcriptional regulators orchestrating cellular identity and function.

B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma.

Current immunotherapy paradigms aim to reinvigorate CD8 T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells.

Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environmental carcinogens or malignant transformation by human papillomavirus (HPV). Here, we assessed the transcriptional profiles of 131,224 single cells from peripheral and intra-tumoral immune populations from patients with HPV and HPV HNSCC and healthy donors. Immune cells within tumors of HPV and HPV HNSCC displayed a spectrum of transcriptional signatures, with helper CD4 T cells and B cells being relatively divergent and CD8+ T cells and CD4+ regulatory T cells being relatively similar.

Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis.

Aim: To evaluate the efficacy, safety, tolerability and steroid-sparing effect of repository corticotropin injection (RCI), in an open-label clinical trial, in refractory adult polymyositis (PM) and dermatomyositis (DM).

Methods: Adults with refractory PM and DM were enrolled by two centres. Inclusion criteria included refractory disease defined as failing glucocorticoid and/or ≥1 immunosuppressive agent, as well as active disease defined as significant muscle weakness and >2 additional abnormal core set measures (CSMs) or a cutaneous 10 cm Visual Analogue Scale score of ≥3 cm at least three other abnormal CSMs.

A Negative Antinuclear Antibody Does Not Indicate Autoantibody Negativity in Myositis: Role of Anticytoplasmic Antibody as a Screening Test for Antisynthetase Syndrome.

Objective: To evaluate the utility of anticytoplasmic autoantibody (anti-CytAb) in antisynthetase antibody-positive (anti-SynAb+) patients.

Methods: Anti-SynAb+ patients were evaluated for antinuclear antibody (ANA) and anti-CytAb [cytoplasmic staining on indirect immunofluorescence (IIF)] positivity. Anti-SynAb+ patients included those possessing anti-Jo1 and other antisynthetase autoantibodies.

Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab.

Objective: The aim was to assess the efficacy of rituximab for the cutaneous manifestations of adult DM and JDM.

Methods: Patients with refractory adult DM (n = 72) and JDM (n = 48) were treated with rituximab in a randomized placebo-phase-controlled trial [either rituximab early drug (week 0/1) or rituximab late arms (week 8/9), such that all subjects received study drug]. Stable concomitant therapy was allowed.

Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

Objectives: To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs).

Methods: Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs.

Anti-signal recognition particle autoantibody ELISA validation and clinical associations.

Objective: The aim of this study was to develop and validate a quantitative anti-signal recognition particle (SRP) autoantibody serum ELISA in patients with myositis and longitudinal association with myositis disease activity.

Methods: We developed a serum ELISA using recombinant purified full-length human SRP coated on ELISA plates and a secondary antibody that bound human IgG to detect anti-SRP binding. Protein immunoprecipitation was used as the gold standard for the presence of anti-SRP.

Anti-transcription intermediary factor 1-gamma autoantibody ELISA development and validation.

Objectives: A quantitative anti-transcription intermediary factor 1-gamma (anti-TIF1-γ) ELISA may improve the detection of cancer-associated myositis (CAM). The aims of this study were the development and validation of a quantitative anti-TIF1-γ autoantibody ELISA in patients with myositis.

Methods: We developed an ELISA using recombinant purified full-length human TIF1-γ.

Macrophages: regulators of sex differences in asthma?

Females are more susceptible to development of asthma than are males. In a mouse model of ovalbumin-induced airway inflammation, with aggravated disease in females compared with males, we studied interactions between immune and resident lung cells during asthma development to elucidate which processes are affected by sex. We studied numbers of regulatory T cells (Tregs), effector T cells, myeloid dendritic cells (mDCs), and alternatively activated macrophages (AAMPhi), and their functional capabilities.

STAT6 activation confers upon T helper cells resistance to suppression by regulatory T cells.

Recent studies have highlighted characteristics of T regulatory cells (Tregs) that underlie their suppressive function. However, mechanisms that override their suppressive function in the context of an adaptive immune response are not well understood. In the lungs of mice undergoing allergic inflammation, appreciable numbers of Tregs were identified that possessed suppressive function when assayed ex vivo.

Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3-mediated suppression of Treg function.

Naturally occurring CD4+CD25+FoxP3+ regulatory T cells (Treg) suppress T helper (Th) cell-mediated immune responses. The cytokines IL-2 and IL-6 are known to influence Treg function. However, their relative effects on Th cells versus Treg are not well understood.

Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-beta.

Studies in humans and mice show an important role for Tregs in the control of immunological disorders. The mechanisms underlying the immunosuppressive functions of Tregs are not well understood. Here, we show that CD4+ T cells expressing Foxp3 and membrane-bound TGF-beta (TGF-beta(m+)Foxp3+), previously shown to be immunosuppressive in both allergic and autoimmune diseases, activate the Notch1-hairy and enhancer of split 1 (Notch1-HES1) axis in target cells.

Hyperresponse to T-cell receptor signaling and apoptosis of Id1 transgenic thymocytes.

The basic helix-loop-helix transcription factors, E2A and HEB, play important roles in T-cell development at multiple checkpoints. Expression of their inhibitor, Id1, abolishes the function of both transcription factors in a dose-dependent manner. The Id1 transgenic thymus is characterized by an accumulation of CD4- CD8- CD44+ CD25- thymocytes, a dramatic reduction of CD4+ CD8+ thymocytes, and an abundance of apoptotic cells.