Mass cytometry reveals systemic and local immune signatures that distinguish inflammatory bowel diseases

Rubin, Samuel J.; Bai, Lawrence; Haileselassie, Yeneneh; Garay, Gladys; Yun, Chohee; Becker, Laren; Streett, Sarah E.; Sinha, S.; Habtezion, Aida

doi:10.1038/s41467-019-10387-7

Cited by 73 publications

(60 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All antibody conjugates were validated for accurate detection of their respective antigens and to ensure minimal isotope spillover by the Stanford HIMC (Supplemental Table 6). Cell thawing and antibody labeling were done following standard protocols 23 (see supplemental materials for details). Approximately 300,000 events or all possible events (whichever lower) were acquired.…”

Section: Methodsmentioning

confidence: 99%

Effects of processing conditions on stability of immune analytes in human blood

Gottfried-Blackmore

Rubin

Bai

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Minimizing variability in collection and processing of human blood samples for research remains a challenge. Delaying plasma or serum isolation after phlebotomy (processing delay) can cause perturbations of numerous analytes. Thus, a comprehensive understanding of how processing delay affects major endpoints used in human immunology research is necessary. Therefore, we studied how processing delay affects commonly measured cytokines and immune cell populations. We hypothesized that short-term time delays inherent to human research in serum and plasma processing impact commonly studied immunological analytes. Blood from healthy donors was subjected to processing delays commonly encountered in sample collection, and then assayed by 62-plex Luminex panel, 40-parameter mass cytometry panel, and 540,000 transcript expression microarray. Variance for immunological analytes was estimated using each individual’s baseline as a control. In general, short-term processing delay led to small changes in plasma and serum cytokines (range − 10.8 to 43.5%), markers and frequencies of peripheral blood mononuclear cell phenotypes (range 0.19 to 3.54 fold), and whole blood gene expression (stable for > 20 K genes)—with several exceptions described herein. Importantly, we built an open-access web application allowing investigators to estimate the degree of variance expected from processing delay for measurements of interest based on the data reported here.

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of processing conditions on stability of immune analytes in human blood

Gottfried-Blackmore

Rubin

Bai

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…A better understanding of the role of the CD27-IgD- population and its subsets seems to be of special interest, since these cells are expanded in various autoimmune diseases, including SLE, 10 rheumatoid arthritis (RA) and inflammatory bowel disease. 29 30…”

Section: Abnormalities Of B Lineage Differentiation In Slementioning

confidence: 99%

Therapeutic implications of the anergic/postactivated status of B cells in systemic lupus erythematosus

et al. 2020

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma cells, atypical CD27-IgD- B cells with increased CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ subsets and anergic CD11c+Tbet+ age-associated B cells. Most findings, together with preclinical lupus models, support the concept of B cell hyperactivity in SLE. However, it remains largely unknown whether these specific B cell subsets have pathogenic consequences and whether they provide relevant therapeutic targets. Recent findings indicate a global distortion of B cell functional capability, in which the entire repertoire of naïve and memory B cells in SLE exhibits an anergic or postactivated (APA) functional phenotype. The APA status of SLE B cells has some similarities to the functional derangement of lupus T cells. APA B cells are characterised by reduced global cytokine production, diminished B cell receptor (BCR) signalling with decreased Syk and Bruton’s tyrosine kinase phosphorylation related to repeated in vivo BCR stimulation as well as hyporesponsiveness to toll-like receptor 9 engagement, but intact CD40 signalling. This APA status was related to constitutive co-localisation of CD22 linked to phosphatase SHP-1 and increased overall protein phosphatase activities. Notably, CD40 co-stimulation could revert this APA status and restore BCR signalling, downregulate protein tyrosine phosphatase transcription and promote B cell proliferation and differentiation. The APA status and their potential rescue by bystander help conveyed through CD40 stimulation not only provides insights into possible mechanisms of escape of autoreactive clones from negative selection but also into novel ways to target B cells therapeutically.

show abstract

“…Unfortunately, the incidence is expected to rise, especially in western countries. IBD is characterized by a diverse set of clinical manifestations, including recurrent diarrhea, hematochezia, and celialgia (Rubin et al, 2019). In addition, it is regarded as a refractory disease by the WHO and currently has little chance of complete cure.…”

Section: Introductionmentioning

confidence: 99%

Sishen Pill Treatment of DSS-Induced Colitis via Regulating Interaction With Inflammatory Dendritic Cells and Gut Microbiota

et al. 2020

View full text Add to dashboard Cite

Sishen Pill (SSP) is a typical prescription in the pharmacopeia of traditional Chinese medicine (TCM), and is usually used to treat inflammatory bowel disease (IBD). It is known that inflammatory dendritic cells (DCs) and imbalance of gut microbiota play significant roles in the pathogenesis of IBD. However, it is not clear whether SSP can treat IBD by regulating interaction of DCs and gut microbiota. In the present study, the levels of inflammatory DCs and gut microbiota were analyzed by flow cytometry and 16S rDNA analysis. SSP relieved the pathological damage to the colon of mice with colitis induced by dextran sodium sulfate (DSS). As typical indicators of inflammatory DCs, the levels of CD11c + CD103 + E-cadherin + cells and pro-inflammatory cytokines [interleukin (IL)-1β,-4,-9, and-17A] were decreased in mice with colitis treated by SSP for 10 days. Simultaneously, the gut microbiota composition was regulated, and beneficial bacteria were increased and pathogenic bacteria were reduced. The results indicated that SSP regulated the interaction between inflammatory DCs and gut microbiota to treat DSS-induced colitis.

show abstract

Mass cytometry reveals systemic and local immune signatures that distinguish inflammatory bowel diseases

Cited by 73 publications

References 59 publications

Effects of processing conditions on stability of immune analytes in human blood

Effects of processing conditions on stability of immune analytes in human blood

Therapeutic implications of the anergic/postactivated status of B cells in systemic lupus erythematosus

Sishen Pill Treatment of DSS-Induced Colitis via Regulating Interaction With Inflammatory Dendritic Cells and Gut Microbiota

Contact Info

Product

Resources

About