Table 4 Key differentially expressed ligands produced by infected immature enterocytes drive the inflammatory process upon SARS-CoV-2 infection.

From: Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways

Ranking

Ligand

Ligand description

Organoid type

Expression change upon SARS-CoV-2 infection

Regulation by cytokines

Known to affect immune cells

Directly explain patients’ blood cytokine levels

1

CXCL2

C-X-C Motif Chemokine Ligand 2

Colonic, Ileal

Up

IFNG, TNF, IL-17, IL-22 (up)

Neutrophils (1,2), fibroblasts, T cells, NK cell and CD8a+ DCs (1), leukocytes (2)

1

CXCL3

C-X-C Motif Chemokine Ligand 3

Colonic, Ileal

Up

TNF, IL-22 (up)

Neutrophils, fibroblasts (1), T cells (2)

1

CXCL10

C-X-C Motif Chemokine Ligand 10

Colonic, Ileal

Up

IFNG, TNF (up)

DC, Th1, NK cells, B cells, monocytes (1), and 29 additional immune cell types (2)

1

CSF1

Colony stimulating factor 1

Colonic

Up

 

35 immune cell types (2)

1

CXCL11

C-X-C Motif Chemokine Ligand 11

Ileal

Up

n.d. (3)

DC (1,2), B cells, NK cells, Th1, monocytes, macrophages (1), lymphocytes, T cells, CD8+ alpha/beta T cell (2)

2

TNFSF13B

TNF Superfamily Member 13b

Ileal

Up

n.d.

B cell, T cell, follicular B cell, naïve B cell, Th17, neutrophils, monocytes (2)

2

LAMC2

Laminin Subunit Gamma 2

Colonic

Down

TNF, IL-22 (up)

  

2

CCL5

C-C Motif Chemokine Ligand 5

Ileal

Up

n.d. (3)

T cells, basophils, eosinophils, macrophages, monocytes, NK cells, DC, Memory T cells, Th1 and Th2 (1), and 23 additional immune cell types (2)

 

2

CX3CL1

C-X3-C Motif Chemokine Ligand 1

Ileal

Up

n.d. (3)

Monocytes, T cells, neutrophil, NK, DC, Mast cells and microglia (1), and 19 additional immune cell types (2)

 

2

CXCL8

C-X-C Motif Chemokine Ligand 8

Ileal

Up

n.d. (3)

Neutrophils, macrophages, basophils, naïve T cells, CD8+ T cells, monocytes (1), and 44 additional immune cell types (2)

 

3

ICAM1

Intercellular Adhesion Molecule 1

Colonic, Ileal

Up

IFNG, TNF, IL-22 (up)

  

3

IL32

Interleukin 32

Colonic

Down

IFNG, TNF (up)

  

3

AREG

Amphiregulin

Colonic

Down

IFNG (up), IL-13 (down)

  

3

TNF

Tumour Necrosis Factor

Colonic, Ileal

Up

TNF, IL-22 (+)

Non-specific: 129 immune cell types (2)

 

3

B2M

Beta-2-immunoglobulin

Colonic, Ileal

Down

IFNG (up)

  

3

HLA-A

Major Histocompatibility Complex, Class I, A

Colonic, Ileal

Down

IFNG (up)

  

3

HLA-B

Major histocompatibility complex, class I, B

Colonic, Ileal

Down

IFNG (up)

  

3

LAMB3

Laminin Subunit Beta 3

Colonic

Down

   
  1. Table showing a list of top-ranked differentially expressed ligands in infected immature enterocytes which were identified to drive inflammation upon SARS-CoV-2 infection. The ranking of the ligands was performed using multiple criteria as explained in the Methods. ‘Organoid type’ indicates whether the expression change of the ligand was found in ileal or colonic infected immature enterocytes upon SARS-CoV-2 infection, respectively. ‘Expression change upon SARS-CoV-2 infection’ indicates the direction of expression change of the ligand in infected immature enterocytes upon SARS-CoV-2 infection. ‘Regulation by cytokines’ indicates whether ligand expression was found to be regulated by cytokines during inflammation based on results from40. Ileal data was not available (n.d.) in this study, so no conclusion could be drawn for ileal ligands. ‘Known to affect immune cells’ indicates whether the ligand was found to be regulated by immune cells using data from ImmunoGlobe41 and ImmuneXpresso42 databases. ‘Directly explain patient blood cytokine levels’ indicates whether the ligand was found to directly regulate blood cytokine levels in COVID-19 patients from5.