Stakeholder Implications of Corporate Sociopolitical Activism

Today’s dynamic market landscape affects and is affected by a variety of significant cultural shifts and touchstones, from global warming and racial injustice, to voter disenfranchisement and the Covid-19 pandemic. In the current dissertation, I examine how firms have expanded their institutional role to address these issues and communicate a sense of moral engagement linked to their brands. I associate these behaviors with a centralized phenomenon—corporate sociopolitical activism (CSA)—which reflects firms’ public speech or actions focused on polarizing issues of societal concern. Such shifts in business behavior coincide with fieldwide conversations among practitioners and scholars about the implied responsibility for broadened social engagement. However, despite the increasing prominence of CSA in the marketplace, the practice has only recently received scholarly attention. In turn, the current dissertation seeks to examine and conceptualize the theoretical, practical, and strategic implications of firms’ activist efforts using a multi-methodological approach. First, Essay I (“‘Focus on Our Cause: How Brand Activism Helps and Hurts Activist Organizations”; under third-round review at the Journal of Consumer Research) utilizes randomized controlled experiments with consequential outcomes to chart the impact of brand activism on consumers’ charitable giving to activist organizations. Next, Essay II (“An Institutional View of Investor Response to Corporate Sociopolitical Activism”; manuscript in progress; targeting the Journal of Marketing) is an event study that examines the moderating effects of issue legitimacy on stock market response to market leaders’ activist efforts

Bordeaux 2018: Wine, Cheese, and γδ T Cells

The 8th “International conference” was held at the University of Bordeaux, 7–10 June 2018. The lead organizer was Julie Déchanet-Merville who together with the other members of the organizing committee; Maria Mamani Matsuda, Matthias Eberl, Myriam Capone, Lionel Couzi, Hannah Kaminski, Layal Massara, Pierre Merville, Sonia Netzer, Angela Pappalardo, Charlotte Domblides, and Vincent Pitard, provided an interesting and exciting programme covering recent progress and developments in all aspects of γδ T cell research. The conference had a very good attendance with 294 delegates from 28 countries on the five continents (Figure 1). In total, 160 abstracts were submitted; resulting in 57 oral presentations and 103 poster presentations. In addition, eight “special lectures” were given after invitation. A “best poster” and “oral presentations” competition was held, covering all sessions, resulting in 10 and 5 awards, respectively (funded by AAI). Thirty-six travel awards were provided for students and post-docs by generous donations from NIH, European Federation of Immunological Societies and Gamma Delta Therapeutics Inc

A comprehensive pathological survey of duodenal biopsies from dogs with diet-responsive chronic enteropathy

Background: The detailed pathological phenotype of diet-responsive chronic enteropathy (CE) and its modulation with dietary therapy remain poorly characterized. Hypothesis/Objectives: Key mucosal lesions of diet-responsive CE resolve with dietary therapy. Methods: This was a prospective observational study of 20 dogs with diet-responsive CE. Endoscopic duodenal biopsies collected before and 6 weeks after the start of a dietary trial were assessed by means of qualitative and quantitative histopathological, immunohistochemical, and ultrastructural criteria. Control duodenal biopsies were obtained from 10 healthy Beagle dogs on 1 occasion. Results: Compared with control dogs, the CE dogs had higher villus stunting scores and higher overall WSAVA scores, a lower villus height-to-width ratio, and higher lamina propria density of eosinophils. The CE dogs also had ultrastructural lesions of the mitochondria and brush border. In common with other studies in which the disease and control populations are not matched for breed, age, sex, and environment, these comparisons should be interpreted with caution. Comparing biopsies collected at presentation and 6 weeks after starting the dietary trial, mean lamina propria mononuclear cell score and lamina propria densities of eosinophils and mononuclear cells decreased. Dietary therapy also improved ultrastructural lesions of the mitochondria and brush border, eliciting a decrease in intermicrovillar space and an increase in microvillus height. Conclusions and Clinical Importance: In dogs with diet-responsive CE, the remission of clinical signs with dietary therapy is associated with subtle decreases in lamina propria density of eosinophils and mononuclear cells, and resolution of ultrastructural lesions of the enterocyte. © 2013 by the American College of Veterinary Internal Medicine

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of gran-uloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracel-lular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adeno-sine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity

Deciphering the complex signalling systems that regulate intestinal epithelial cell death processes and shedding

Intestinal epithelial cells play a fundamental role in maintaining homeostasis. Shedding of intestinal cells in a controlled manner is critical to maintenance of barrier function. Barrier function is maintained during this shedding process by a redistribution of tight junctional proteins to facilitate closure of the gap left by the shedding cell. However, despite the obvious importance of epithelial cell shedding to gut health a central question is how the extrusion of epithelial cells is achieved, enabling barrier integrity to be maintained in the healthy gut and restored during inflammation remains largely unanswered. Recent studies have provided evidence that excessive epithelial cell shedding and loss of epithelial barrier integrity is triggered by exposure to lipopolysaccharide (LPS) or tumour necrosis factor (TNF). Subsequent studies have provided evidence of the involvement of specific cellular components and signalling mechanisms as well as the functionality of microbiota that can be either detrimental or beneficial for intestinal barrier integrity. This review, will focus on the evidence and decipher how the signalling systems through which the mucosal immune system and microbiota can regulate epithelial cell shedding and how these mechanisms interact to preserve the viability of the epithelium

Bifidobacterium breve UCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells

The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA-Seq, and differentially expressed genes, pathways and affected cell types determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways were observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies

The microbiome activates CD4 T-cell-mediated immunity to compensate for increased intestinal permeability

Background & Aims: Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK). Here we asked whether constitutive tight junction barrier loss impacts susceptibility to enteric pathogens. Methods: Acute or chronic Toxoplasma gondii or Salmonella typhimurium infection was assessed in CA-MLCK transgenic or wild-type mice. Germ-free mice or those lacking specific immune cell populations were used to investigate the effect of microbial-activated immunity on pathogen translocation in the context of increased intestinal permeability. Results: Acute T gondii and S typhimurium translocation across the epithelial barrier was reduced in CA-MLCK mice. This protection was due to enhanced mucosal immune activation that required CD4^+ T cells and interleukin 17A but not immunoglobulin A. The protective mucosal immune activation in CA-MLCK mice depended on segmented filamentous bacteria (SFB), because protection against early S typhimurium invasion was lost in germ-free CA-MLCK mice but could be restored by conventionalization with SFB-containing, not SFB-deficient, microbiota. In contrast, chronic S typhimurium infection was more severe in CA-MLCK mice, suggesting that despite activation of protective mucosal immunity, barrier defects ultimately result in enhanced disease progression. Conclusions: Increased epithelial tight junction permeability synergizes with commensal bacteria to promote intestinal CD4^+ T-cell expansion and interleukin 17A production that limits enteric pathogen invasion

Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes

In human intestinal epithelial crypt (HIEC) cells, the PI3-K/Akt-1 pathway is crucial for the promotion of cell survival and suppression of anoikis. Class I PI3-K consists of a complex formed by a catalytic (C) and regulatory (R) subunit. Three R (p85α, β, and p55γ) and four C (p110α, β, γ and δ) isoforms are known. Herein, we analyzed the expression of PI3-K isoforms in HIEC cells and determined their roles in cell survival, as well as in the β1 integrin/Fak/Src-mediated suppression of anoikis. We report that: (1) the predominant PI3-K complexes expressed by HIEC cells are p110α/p85β and p110α/p55γ; (2) the inhibition and/or siRNA-mediated expression silencing of p110α, but not that of p110β, γ or δ, results in Akt-1 down-activation and consequent apoptosis; (3) the expression silencing of p85β or p55γ, but not that of p85α, likewise induces Akt-1 down-activation and apoptosis; however, the impact of a loss of p55γ on both Akt-1 activation and cell survival is significantly greater than that from the loss of p85β; and (4) both the p110α/p85β and p110α/p55γ complexes are engaged by β1 integrin/Fak/Src signaling; however, the engagement of p110α/p85β is primarily Src-dependent, whereas that of p110α/p55γ is primarily Fak-dependent (but Src-independent). Hence, HIEC cells selectively express PI3-K isoform complexes, translating into distinct roles in Akt-1 activation and cell survival, as well as in a selective engagement by Fak and/or Src within the context of β1 integrin/Fak/Src-mediated suppression of anoikis