Induction of High Endothelial Venule-like Vessels in Oral and Cutaneous Lichen Planus: A Comparative Study

Abstract

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease involving the oral mucosa and skin. Both oral LP (OLP) and cutaneous LP (CLP) are histopathologically characterized by dense subepithelial lymphocyte infiltrates; however, the mechanisms underlying lymphocyte recruitment to sites of LP lesions are not fully understood. Here, we assessed the induction of peripheral lymph node addressin (PNAd)-expressing high endothelial venule (HEV)-like vessels in 19 OLP and 17 CLP cases. To do so, we performed immunohistochemical staining for PNAd and CD34, followed by quantitative analysis. We also conducted triple immunohistochemistry for PNAd and either CD3 and CD20 or CD4 and CD8 to identify the lymphocyte subset preferentially recruited via HEV-like vessels. PNAd-expressing HEV-like vessels were induced in and around lymphocyte aggregates in all cases of OLP and in 10 of 17 CLP cases, and these vessels were more frequently observed in OLP relative to CLP. Although the number of T-cells attached per HEV-like vessel exceeded the number of B-cells in both OLP and CLP, the number of CD4⁺ T-cells attached was greater than the number of CD8⁺ T-cells only in OLP. These findings combined suggest that PNAd-expressing HEV-like vessels play a more important role in the pathogenesis of OLP compared with CLP.

Keywords: chronic inflammation; high endothelial venule (HEV); lichen planus; lymphocyte recruitment; peripheral lymph node addressin (PNAd).

Figure 1.

Histopathology of OLP (middle panel) and CLP (right panel). Intact oral mucosa tissues served as controls (left panel). Note that subepithelial band-like lymphocyte infiltrates are common in both types of LP. Insets indicate keratinocyte apoptosis (Civatte bodies). Scale bar = 100 µm for main pictures and 20 µm for insets. Abbreviations: LP = lichen planus; OLP = oral LP; CLP = cutaneous LP.

Figure 2.

Induction of HEV-like vessels in OLP and CLP. Serial tissue sections were stained with H&E and immunostained for CD34 and PNAd. HEV-like vessels positive for PNAd are seen in and around lymphocyte aggregates formed in OLP and CLP. These HEV-like vessels are not observed in intact oral mucosa. Scale bar = 50 µm. Abbreviations: H&E = hematoxylin and eosin; HEV = high endothelial venule; LP = lichen planus; OLP = oral LP; CLP = cutaneous LP; PNAd = peripheral lymph node addressin.

Figure 3.

Differences in the PNAd⁺/CD34⁺ vessel ratio in OLP (n=19) and CLP (n=17). The PNAd⁺/CD34⁺ vessel ratio in OLP significantly exceeds that seen in CLP. Data are presented as means with SD. Abbreviations: LP = lichen planus; OLP = oral LP; CLP = cutaneous LP.

Figure 4.

Lymphocyte subsets attached to the luminal aspect of HEV-like vessels induced in OLP and CLP. (A) Triple immunohistochemistry for PNAd (brown), CD3 (blue), and CD20 (red). Both T-cells (arrow) and B-cells (arrowhead) attach to the luminal aspect of HEV-like vessels. Scale bar = 50 µm. (B) The number of respective T and B cells attached per HEV-like vessel. Data are presented as means with SD. Abbreviations: HEV = high endothelial venule; LP = lichen planus; OLP = oral LP; CLP = cutaneous LP; PNAd = peripheral lymph node addressin.

Figure 5.

T-cell subsets attached to the luminal aspect of HEV-like vessels induced in OLP and CLP. (A) Triple immunohistochemistry for PNAd (brown), CD4 (blue), and CD8 (red). Both CD4⁺ (arrow) and CD8⁺ T cells (arrowhead) attach to the luminal aspect of HEV-like vessels. Scale bar = 50 µm. (B) The number of respective CD4⁺ and CD8⁺ T cells attached per HEV-like vessel. Data are presented as means with SD. Abbreviations: HEV = high endothelial venule; LP = lichen planus; OLP = oral LP; CLP = cutaneous LP; PNAd = peripheral lymph node addressin.