Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.

Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103γδ T cell restoration was associated with sustained inflammatory bowel disease remission.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A dynamic COVID-19 immune signature includes associations with poor prognosis.

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies.

Managing Pervasive Sensing Campaigns via an Experimentation-as-a-Service Platform for Smart Cities.

The adoption of technologies like the IoT in urban environments, together with the intensive use of smartphones, is driving transformation towards smart cities. Under this perspective, Experimentation-as-a-Service within OrganiCity aims to create an experimental facility with technologies, services, and applications that simplify innovation within urban ecosystems. We discuss here tools that facilitate experimentation, implementing ways to organize, execute, and administer experimentation campaigns in a smart city context.

Co-Creating the Cities of the Future.

In recent years, the evolution of urban environments, jointly with the progress of the Information and Communication sector, have enabled the rapid adoption of new solutions that contribute to the growth in popularity of Smart Cities. Currently, the majority of the world population lives in cities encouraging different stakeholders within these innovative ecosystems to seek new solutions guaranteeing the sustainability and efficiency of such complex environments. In this work, it is discussed how the experimentation with IoT technologies and other data sources form the cities can be utilized to co-create in the OrganiCity project, where key actors like citizens, researchers and other stakeholders shape smart city services and applications in a collaborative fashion.

Reconstruction of the experimentally supported human protein interactome: what can we learn?

Background: Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of their networks vary depending on the PPI data combined. Due to this inherent heterogeneity, the way in which the human PPI network expands via multiple dataset integration has not been comprehensively analyzed.

The inter-relatedness and interdependence of mouse T cell receptor gammadelta+ and alphabeta+ cells.

Although T cell receptor (TCR)gammadelta+ and TCRalphabeta+ cells are commonly viewed as functionally independent, their relatedness and potential interdependence remain enigmatic. Here we have identified a gene profile that distinguishes mouse gammadelta cell populations from conventional alphabeta T cells. However, this profile was also expressed by sets of unconventional alphabeta T cells.

Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants.

The intraepithelial lymphocyte (IEL) network of T-cell receptor gammadelta+ (Vgamma5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-beta4 (Tbeta4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UTbeta4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LTbeta4) with unknown bioactivity. Freshly isolated Vgamma5+ DETCs expressed both forms, while only LTbeta4 was preferentially up-regulated after cellular activation in vitro.

Intraepithelial lymphocytes: exploring the Third Way in immunology.

Locally resident intraepithelial lymphocytes (IELs) are primarily T cells with potent cytolytic and immunoregulatory capacities, which they use to sustain epithelial integrity. Here, we consider that most IEL compartments comprise a variable mixture of two cell types: T cells primed to conventional antigen in the systemic compartment and T cells with ill-defined reactivities and origins, whose properties seem to place them mid-way between the adaptive and innate immune responses. We review the capacity of IELs to limit the dissemination of infectious pathogens and malignant cells and to control the infiltration of epithelial surfaces by systemic cells.

Biological insights into TCRgammadelta+ and TCRalphabeta+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE).

Intraepithelial lymphocytes (IELs) are abundant, evolutionarily conserved T cells, commonly enriched in T cell receptor (TCR) gammadelta expression. However, their primary functional potential and constitutive activation state are incompletely understood. To address this, serial analysis of gene expression (SAGE) was applied to murine TCRgammadelta+ and TCRalphabeta+ intestinal IELs directly ex vivo, identifying 15,574 unique transcripts that collectively portray an "activated yet resting," Th1-skewed, cytolytic, and immunoregulatory phenotype applicable to multiple subsets of gut IELs.

The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15.

Glucocorticoids are agents endowed with powerful immunosuppressive and anti-inflammatory properties partially related to the inhibition of adhesion-related processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and CD2 expression in human peripheral blood mononuclear cells (PBMC) by down-regulating mRNA steady-state levels. In this study, we investigated whether glucocorticoids could also act indirectly by modulating the effect/function of cytokines whose expression are known to inhibit.

Overrepresentation of the Fcgamma receptor type IIA R131/R131 genotype in caucasoid systemic lupus erythematosus patients with autoantibodies to C1q and glomerulonephritis.

Objective: To test the hypothesis that there is an association between the Fcgamma receptor type IIA (FcgammaRIIA)-H/R131 polymorphism and autoantibodies to the collagenous region (CLR) of C1q in patients with systemic lupus erythematosus (SLE).

Methods: One hundred ninety-five Caucasoid lupus patients were studied. Anti-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and FcgammaRIIA genotype analysis was performed by polymerase chain reaction.

A targeted disruption of the murine complement factor B gene resulting in loss of expression of three genes in close proximity, factor B, C2, and D17H6S45.

Factor B is a serine protease, essential for the function of the alternative pathway of complement activation. To study further the importance of the alternative pathway of complement activation in vivo and to help elucidate any additional functions of factor B or its activation fragments we developed, by homologous recombination in embryonic stem cells, mice with a disrupted factor B gene. Factor B-deficient mice produced no detectable factor B mRNA or protein and had no detectable factor B enzymatic activity or alternative pathway function in their serum.

Fc gamma RIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease.

An allotypic variant of Fc gamma RIIa, Fc gamma RIIa-HR (Fc gamma RIIa-R131), has been shown in vitro to reduce the capacity of phagocytic cells to bind and internalize IgG-containing immune complexes. Our aim was to determine whether this allotypic variant was associated with susceptibility to SLE and the development of lupus nephritis, as previous studies have suggested. Fc gamma RIIA genotype analysis was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 215 Caucasoid, 70 Afro-Caribbean, and 46 Chinese patients with SLE, and in 259,77 and 49 ethnically matched controls, respectively.

The molecular basis of hereditary complement factor I deficiency.

The molecular basis of hereditary complement factor I deficiency is described in two pedigrees. In one pedigree, there were two factor I-deficient siblings, one of whom was asymptomatic and the other suffered from recurrent pyogenic infections. Their factor I mRNA was analyzed by reverse transcription of fibroblast RNA followed by amplification using the polymerase chain reaction.