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Review
. 2021 Oct 12;10(20):4667.
doi: 10.3390/jcm10204667.

Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis

Jun Zhu  1   2 , Takenori Inomata  1   3   4   5   6 , Antonio Di Zazzo  7 , Koji Kitazawa  8   9 , Yuichi Okumura  1   3   5 , Marco Coassin  7 , Pier Luigi Surico  7 , Kenta Fujio  1   5 , Ai Yanagawa  5 , Maria Miura  1   5 , Yasutsugu Akasaki  1   5 , Keiichi Fujimoto  5   6 , Ken Nagino  4 , Akie Midorikawa-Inomata  4 , Kunihiko Hirosawa  1   5 , Mizu Kuwahara  1   5 , Tianxiang Huang  1   5 , Hurramhon Shokirova  1 , Atsuko Eguchi  4 , Akira Murakami  1   5   6
Affiliations
Review

Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis

Jun Zhu et al. J Clin Med. .

Abstract

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.

Keywords: adaptive immunity; corneal transplantation; diversity; heterogeneity; immune cell; innate immunity; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the studies selected for meta-analysis.
Figure 2
Figure 2
The role of the dendritic cells in allograft survival. (A) Immature dendritic cells promote allograft survival; (B) Langerhans cells increase the allograft rejection rate. CI, confidence intervals; EV, event; Trt, treatment; Ctrl, control.
Figure 3
Figure 3
Effects of cytokines in immunotherapies for corneal allografts. (A) IL-1RA promotes allograft survival. (B) Anti-IL-17 antibody increased allograft rejection. (C) Anti-VEGF improves allograft survival rate. (D) Local administration of IL-10 did not improve allograft survival. CI, confidence intervals; EV, event; Trt, treatment; Ctrl, control.
Figure 4
Figure 4
Blockage of co-stimulatory pathways influences corneal-allograft survival. (A) CLTA-4 Ig promotes allograft survival. (B) Anti-CD154 antibody increases the allograft survival rate. (C) CCR7-CCL19 blockade improves the allograft survival rate. CI, confidence intervals; EV, event; Trt, treatment; Ctrl, control.
Figure 5
Figure 5
Regulatory T cells prolong corneal allograft survival. CI, confidence intervals; EV, event; Trt, treatment; Ctrl, control.
Figure 6
Figure 6
Inflammatory cytokine level in the aqueous humor of human corneal graft cases. (A) In the survival group, the level of TNF-α was 1.29 pg/mL (95% CI, 0.65 to 1.94 pg/mL). (B) IFN-γ was 1.67 pg/mL (95% CI, 0.90 to 2.44 pg/mL), (C) IL-1β was 2.76 pg/mL (95% CI, 0.49 to 5.03 pg/mL), and (D) IL-2 was 1.44 pg/mL (95% CI, 0.60 to 2.27 pg/mL). CI, confidence intervals.
Figure 7
Figure 7
Cells, cell membrane receptors, ligands, and cytokines form the immune pathway involved in corneal graft survival.
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