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Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT. T cell receptor (TCR) repertoire profiling demonstrated that islet Treg clonotypes are expanded in the islets, suggesting localized antigen-driven expansion in inflamed islets. To determine their specificity, we captured TCRαβ pairs from islet Tregs using single-cell TCR sequencing and found direct evidence that some of these TCRs were specific for islet-derived antigens including insulin B:9-23 and proinsulin. Consistently, insulin B:9-23 tetramers readily detected insulin-specific Tregs in the islets of NOD mice. Lastly, islet Tregs from prediabetic NOD mice were effective at preventing diabetes in Treg-deficient NOD.CD28-/- recipients. These results provide a glimpse into the specificities of Tregs in a natural repertoire that are crucial for opposing the progression of autoimmune diabetes.

In NOD mice, CD11c+ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c+ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c+ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c+ cells was partially dependent on their receptor Ccr5. Treatment with islet Ag-specific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c+ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.

We examined the anticipatory stress response in musicians before a day of rehearsal and a concert and examined if experience levels modulated physiological and perception of stress responses. Twenty members of a professional orchestra had their heart rate (HR), blood pressure (BP), and galvanic skin response/conductance (GSR) measured as well as self-assessment of their anxiety surrounding their performance. HR was significantly elevated prior to a concert (87 bpm) compared with a rehearsal (80 bpm), whereas no differences were observed for BP. GSR responses prior to a concert were significantly elevated in less experienced musicians compared with their more experienced peers and a significant inverse correlation was also found between years of experience and GSR responses. Similarly, musicians with greater experience reported on average less perceived somatic anxiety during the concert and a significant inverse correlation was found between years of experience and perceived somatic anxiety. These results suggest that the type of performance and the experience level of the musician modulates anticipatory stress responses. Further understanding of the role of anticipatory stress in musicians could have a number of practical benefits. [ABSTRACT FROM AUTHOR]

Genetic and cellular studies of type 1 diabetes in patients and in the nonobese diabetic mouse model of type 1 diabetes point to an imbalance between effector T cells and regulatory T cells (Tregs) as a driver of the disease. The imbalance may arise as a consequence of genetically encoded defects in thymic deletion of islet antigen-specific T cells, induction of islet antigen-specific thymic Tregs, unfavorable tissue environment for peripheral Treg induction, and failure of islet antigen-specific Tregs to survive in the inflamed islets secondary to insufficient IL-2 signals. These understandings are the foundation for rationalized design of new therapeutic interventions to restore the balance by selectively targeting effector T cells and boosting Tregs.

Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Treg lineage commitment and functional stability are influenced by selected extracellular signals from the local environment, shaped by distinctive intracellular signaling network, and secured by their unique epigenetic profile. Recent advances in our understanding of the complex processes of Treg lineage differentiation, maintenance, and function has paved the way for developing strategies to manipulate these important cells for therapeutic benefit in many diseases. In this review, we will summarize recent advances in our understanding of Treg biology as well as Treg-targeted therapies in the context of autoimmune disease.

Introduction: We established the most common cutaneous diseases that received dermatology consultation in the adult emergency department (ED) and identified differentiating clinical characteristics of dermatoses that required hospital admission.Methods: A retrospective chart review of 204 patients presenting to the ED who received dermatology consultations at Los Angeles County/University of Southern California Medical Center, an urban tertiary care teaching hospital.Results: Of all patients, 18% were admitted to an inpatient unit primarily for their cutaneous disease, whereas 82% were not. Of nonadmitted patients, the most commonly diagnosed conditions were eczematous dermatitis not otherwise specified (8.9%), scabies (7.2%), contact dermatitis (6.6%), cutaneous drug eruption (6.0%), psoriasis vulgaris (4.2%), and basal cell carcinoma (3.6%). Of patients admitted for their dermatoses, the most highly prevalent conditions were erythema multiforme major/Stevens-Johnson syndrome (22%), pemphigus vulgaris (14%), and severe cutaneous drug eruption (11%). When compared with those of nonadmitted patients, admitted skin conditions were more likely to be generalized (92% vs 72%; P = 0.0104), acute in onset (< 1 month duration) (81% vs 51%; P = 0.0005), painful (41% vs 15%; P = 0.0009), blistering (41% vs 7.8%; P < 0.0001), and ulcerated or eroded (46% vs 7.8%; P < 0.0001). They were more likely to involve the mucosa (54% vs 7.2%; P < 0.0001) and less likely to be pruritic (35% vs 58%; P = 0.0169).Conclusion: We have described a cohort of patients receiving dermatologic consultation in the ED of a large urban teaching hospital. These data identify high-risk features of more severe skin disease and may be used to refine curricula in both emergency and nonemergency cutaneous disorders for emergency physicians. [West J Emerg Med. 2011;12(4):551–555.]

The struggles and stressors that new faculty members face have been well documented, but during our first year at a Jesuit institution, we encountered unexpected, unprecedented challenges beyond typical. Fortunately, we developed a unique sense of community as new faculty stemming from Regis University's Manresa Experience. The Manresa Experience exposed us to Jesuit values, provided networking opportunities with colleagues, and introduced a togetherness that would help unite us against two unforgiving viruses. The first virus plagued Regis University in Fall 2019, when a cyberattack crippled our entire network security. As new faculty members, we were unable to utilize valuable resources that would normally aid in our successful transition to a new university. Almost immediately following this cyberattack, Regis University faced the tremendous challenges surrounding the COVID-19 global pandemic, which forced us to transition our teambased learning pedagogy into an online platform within a matter of days. The Manresa Experience and Jesuit values supported us in unexpected ways despite these extraordinary circumstances. Individually, we experienced the challenges in our own unique context. Together, we found peace amidst the turmoil and success amongst the chaos as we all relied on the Jesuit values and our support system created by the Manresa Experience. [ABSTRACT FROM AUTHOR]