Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection

Abstract The coronavirus SARS-CoV-2 contributes to morbidity and mortality mainly as a result of immune-pathology in the lungs. Recent data has shown multi-system involvement with widespread viral tropism. Here we present a detailed intestinal protein characterisation of SARS-Cov-2 entry molecules ACE2 and TMPRSS2 in patients with Inflammatory Bowel Disease ([IBD]; Ulcerative Colitis [UC] and Crohn’s disease [CD]) with age- and sex-match non-IBD controls; and in those with fatal COVID19 infection. Our study showed that IBD gut inflammation did not influence ACE2 and TRPMSS2 expression. Of interest, colonic protein expression of ACE2 and TRPMSS2 are cytoplasmic distinct to the membranous pattern in the ileum. We observed a significant increase in immune cells within the lamina propria in UC and CD that expressed ACE2 and TRMPSS2 when compared to non-IBD controls. These were identified as plasma cells with multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) expression. In six fatal COVID19 cases, there was no gut inflammation despite evidence of viral tropism within the enterocytes. Our data provides evidence for tissue expression of entry molecules ACE2 and TMPRSS2 including a close apposition to plasma cells – both pointing towards a role of the gut in the immune response to SARS-CoV-2 infection.

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Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection

Inflammation ◽

10.1007/s10753-021-01567-z ◽

2021 ◽

Author(s):

Milly J. McAllister ◽

Kathryn Kirkwood ◽

Shaun C. Chuah ◽

Emily J. Thompson ◽

Jennifer A. Cartwright ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Lamina Propria ◽

Bowel Disease ◽

Plasma Cells ◽

Staining Intensity ◽

Tissue Expression ◽

Viral Tropism ◽

Intestinal Protein ◽

Inflammatory Bowel ◽

Protein Characterisation

Abstract—The coronavirus SARS-CoV-2 contributes to morbidity and mortality mainly as a result of immune-pathology in the lungs. Recent data has shown multi-system involvement with widespread viral tropism. Here we present a detailed intestinal protein characterisation of SARS-Cov-2 entry molecules ACE2 and TMPRSS2 in patients with inflammatory bowel disease ([IBD]; ulcerative colitis [UC] and Crohn’s disease [CD]) with age- and sex-matched non-IBD controls, and in those with fatal COVID-19 infection. In our dataset, ACE2 and TMPRSS2 displayed a membrane enterocyte staining in the ileum (due to presence of brush border/microvilli) in contrast to a cytoplasmic pattern in the colon. We also showed a high ACE2/low TMPRSS2 expression pattern in the ileum with a reverse trend in the colon. In UC, colonic ACE2 and TMPRSS2 are cytoplasmic in nature, with significantly higher ACE2 staining intensity compared to non-IBD controls. In inflamed and unaffected IBD mucosa, ileal and colonic enterocyte ACE2 and TMPRSS2 expressions are not modified in the histologic presence of inflammation. We observed immune cells within the lamina propria that expressed ACE2 and TMPRSS2, at higher frequencies in IBD when compared to non-IBD controls. These were identified as plasma cells with multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) expression. We further analysed the gut histology of six fatal COVID-19 cases, with no difference in colonic and ileal ACE2/TMRPSS2 staining (compared to non-IBD controls) and identified ACE2 + lamina propria plasma cells. Of interest, in this COVID-19 cohort, there was no histologic evidence gut inflammation despite known evidence of viral tropism within the enterocytes. Our data provides evidence for tissue expression of entry molecules ACE2 and TMPRSS2 including a close apposition to plasma cells — both pointing towards a role of the gut in the antecedent immune response to SARS-CoV-2 infection.

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Effects of Taste Signaling Protein Abolishment on Gut Inflammation in an Inflammatory Bowel Disease Mouse Model

Journal of Visualized Experiments ◽

10.3791/58668 ◽

2018 ◽

Cited By ~ 2

Author(s):

Ya-Wen Du ◽

Qun Liu ◽

Xiao-Cui Luo ◽

Dong-Xiao Zhao ◽

Jian-Bo Xue ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Gut Inflammation ◽

Signaling Protein ◽

Inflammatory Bowel

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TRAIL suppresses gut inflammation and inhibits colitogeic T-cell activation in experimental colitis via an apoptosis-independent pathway

Mucosal Immunology ◽

10.1038/s41385-019-0168-y ◽

2019 ◽

Vol 12 (4) ◽

pp. 980-989 ◽

Cited By ~ 6

Author(s):

I. T. Chyuan ◽

H. F. Tsai ◽

C. S. Wu ◽

P. N. Hsu

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

T Cell Activation ◽

Bowel Disease ◽

Cell Activation ◽

Gut Inflammation ◽

Inflammatory Bowel ◽

Colitis Model

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease.

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Inflammatory bowel disease and biomarkers of gut inflammation and permeability in a community with high exposure to perfluoroalkyl substances through drinking water

Environmental Research ◽

10.1016/j.envres.2019.108923 ◽

2020 ◽

Vol 181 ◽

pp. 108923 ◽

Cited By ~ 6

Author(s):

Yiyi Xu ◽

Ying Li ◽

Kristin Scott ◽

Christian H. Lindh ◽

Kristina Jakobsson ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Drinking Water ◽

Bowel Disease ◽

Perfluoroalkyl Substances ◽

High Exposure ◽

Gut Inflammation ◽

Inflammatory Bowel

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Dysregulation of Intestinal Mucosal Immunity: Implications in Inflammatory Bowel Disease

Physiology ◽

10.1152/physiologyonline.2001.16.6.272 ◽

2001 ◽

Vol 16 (6) ◽

pp. 272-277 ◽

Cited By ~ 2

Author(s):

F. Stephen Laroux ◽

Kevin P. Pavlick ◽

Robert E. Wolf ◽

Matthew B. Grisham

Keyword(s):

Inflammatory Bowel Disease ◽

Immune System ◽

Mucosal Immunity ◽

Immune Regulation ◽

Bowel Disease ◽

Mucosal Immune System ◽

Gut Inflammation ◽

Inflammatory Bowel ◽

Efficient Mechanisms

The mucosal interstitia of the intestine and colon are continuously exposed to large amounts of dietary and microbial antigens. Fortunately, the mucosal immune system has evolved efficient mechanisms to distinguish potentially pathogenic from nonpathological antigens. There are, however, situations in which this immune regulation fails, resulting in chronic gut inflammation.

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