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Review
. 2023 Jul 3:14:1219907.
doi: 10.3389/fimmu.2023.1219907. eCollection 2023.

TNF superfamily control of tissue remodeling and fibrosis

Hope Steele  1   2 , Jason Cheng  1 , Ashley Willicut  3 , Garrison Dell  1   2 , Joey Breckenridge  1   2 , Erica Culberson  3 , Andrew Ghastine  1 , Virginie Tardif  4 , Rana Herro  1   5
Affiliations
Review

TNF superfamily control of tissue remodeling and fibrosis

Hope Steele et al. Front Immunol. .

Abstract

Fibrosis is the result of extracellular matrix protein deposition and remains a leading cause of death in USA. Despite major advances in recent years, there remains an unmet need to develop therapeutic options that can effectively degrade or reverse fibrosis. The tumor necrosis super family (TNFSF) members, previously studied for their roles in inflammation and cell death, now represent attractive therapeutic targets for fibrotic diseases. In this review, we will summarize select TNFSF and their involvement in fibrosis of the lungs, the heart, the skin, the gastrointestinal tract, the kidney, and the liver. We will emphasize their direct activity on epithelial cells, fibroblasts, and smooth muscle cells. We will further report on major clinical trials targeting these ligands. Whether in isolation or in combination with other anti-TNFSF member or treatment, targeting this superfamily remains key to improve efficacy and selectivity of currently available therapies for fibrosis.

Keywords: TNF superfamily; TNFSF; fibrosis; mucosa; remodeling.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
TNFSF contribution to fibrosis across human organs. Overview of contribution of TNFSF members in driving fibrotic disease in the lungs, heart, skin, kidneys, liver, and gastrointestinal tract based on current literature. Figure was created with BioRender.com.
Figure 2
Figure 2
TNF Superfamily Member Activity on Structural and Immune Cells. TNFSF members can exert direct activities on structural and immune cells to perpetuate fibrosis. Figure was created with BioRender.com.
Figure 3
Figure 3
TNFα Activity on Structural and Immune Cells. TNFα (TNFSF2) can act directly on structural cells (fibroblasts) and immune cells (macrophages, T cells) to drive pro-fibrotic and anti-fibrotic effects. Figure was created with BioRender.com.
Figure 4
Figure 4
LIGHT Activity on Structural and Immune Cells. LIGHT (TNFSF14) can act directly on structural cells (epithelial cells, smooth muscle cells, fibroblasts) and immune cells (granulocytes, macrophages) to drive pro-fibrotic and anti-fibrotic effects. Figure was created with BioRender.com.
Figure 5
Figure 5
TL1A Activity on Structural and Immune Cells. TL1A (TNFSF15) can act directly on structural cells (epithelial cells, fibroblasts) and immune cells (macrophages, T cells, ILC2s) to drive pro-fibrotic and anti-fibrotic effects. Figure was created with BioRender.com.
Figure 6
Figure 6
BAFF Activity on Structural and Immune Cells. BAFF (TNFSF13B) can act directly on structural cells (fibroblasts) and immune cells (B cells) to drive pro-fibrotic and anti-fibrotic effects. Figure was created with BioRender.com.
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Publication types

Grants and funding

This work was supported by funds from the Center for Inflammation and Tolerance (CIT) at CCHMC to R.H., the Praespero Foundation to R.H., and the Cancer Free Kids Foundation to R.H.

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