Table 1.
Summary of interleukin (IL)-36/IL-36 receptor (IL-36R) mediated tissue fibrosis.
| Organ | Disease Model | IL-36R Ligand Involved | IL-36 Producing Cells | Possible Downstream Targets | Outcome of IL-36R Inhibition | Refs |
|---|---|---|---|---|---|---|
| Lung | Bleomycin induced IPF | IL-36γ | IL-17A expressing Macrophages (CD9hi, IL3γ+) |
Th17 T cells | IL-38 overexpression reduced lung inflammation, IL-17A production, and fibrosis | [88,90] |
| Kidney | UUO | IL-36α | Renal TECs | BMDCs, Th17 T cells | IL-36R KO prevented T cell activation/infiltration, and suppressed the occurrence of renal TILs | [21] |
| Heart | LAD coronary artery ligation model of MI | IL-38 | Cardiomyocytes | DCs | Recombinant IL-38 treatment protected against cardiac fibrosis and cardiomyocyte apoptosis. IL-38 also altered DC differentiation and T cell responses |
[89] |
| Intestine | DSS and TNBS induced intestinal colitis and fibrosis | IL-36α | CD14+CD64+ CD163+
Macrophages |
α-SMA+ Fibroblasts | IL-36R KO protected mice from colitis and fibrosis. IL-36R deficiency also reduced collagen production and blunted the presence of activated fibroblasts (CD90+, α-SMA+) |
[87] |
| Pancreas | Chronic Pancreatitis | IL-36α | -------- | Myofibroblasts | --------- | [120] |
Bone marrow-derived dendritic cells (BMDCs); dendritic cells (DCs); dextran sulfate sodium salt (DSS); idiopathic pulmonary fibrosis (IPF); knockout (KO); left anterior descending (LAD); myocardial infarction (MI); T helper 17 (TH17); 2,4,6-trinitro benzene sulfonic acid (TNBS); tubular epithelial cells (TECs); tubulointerstitial lesions (TILs); unilateral ureteral obstruction (UUO).