Thymic Stromal Lymphopoietin Is Implicated in the Pathogenesis of Bullous Pemphigoid by Dendritic Cells

Abstract

Objectives. Both thymic stromal lymphopoietin (TSLP) and dendritic cells (DCs) are involved in many autoimmune diseases, but the potential roles of TSLP and DCs in bullous pemphigoid (BP) have not been clarified. We sought to explore the contributions of TSLP and DCs in patients with BP. Methods. TSLP levels in sera and blister fluids were measured by enzyme-linked immunosorbent assay. The TSLP expression in the BP lesional skin was detected by immunohistochemical staining. Infiltration of DCs, marked by DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its relationship with TSLP and TSLP receptors was evaluated by immunofluorescence staining. Results. We found that TSLP levels in sera and in blister fluids of patients with BP were higher compared to the control groups. In patients with BP, TSLP levels in sera correlated with TSLP levels in blisters. The expression of TSLP in the BP lesional skin was higher compared to the healthy controls’ skin. Greater numbers of TSLP-positive cells were observed in the epidermis of patients with BP compared to the healthy controls. Greater numbers of DC-SIGN-positive cells were present in the BP lesional skin compared to the skin of controls. The expression of TSLP was highly upregulated in DC-SIGN-positive cells, and most DC-SIGN-positive cells expressed TSLP receptors. Conclusions. We conclude that TSLP may activate DC-SIGN-positive DCs directly, which may be involved in the pathogenesis of BP.

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

“…The pathophysiology of BP is still unclear, but autoantibodies to structured proteins in the dermal-epidermal junction and Th2 immunity are likely involved in this disorder ( 81 , 82 ). Multiple studies have identified a markedly increased concentration of TSLP in skin lesions, blister fluid, and sera of patients with BP, especially in the lower layer of the epidermis ( 83 – 86 ). Furthermore, the levels of TSLP in serum correlated with those in blisters ( 86 ).…”

“…Multiple studies have identified a markedly increased concentration of TSLP in skin lesions, blister fluid, and sera of patients with BP, especially in the lower layer of the epidermis ( 83 – 86 ). Furthermore, the levels of TSLP in serum correlated with those in blisters ( 86 ). These findings imply that TSLP is involved in the immunopathogenesis of BP and could be released by keratinocytes in the epidermis of BP.…”

“…Li et al showed that the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-positive DCs in BP lesional skin was higher than that in healthy controls and correlated with more robust TSLP expression in the epidermis and blisters of BP patients ( 86 ). In comparison, Langerhans cells (LCs) in the epidermis of BP lesional skin were less likely to be associated with increased TSLP expression ( 86 ). Moreover, DC-SIGN-positive DCs, but not LCs, expressing langerin, were positive for TSLPR ( 86 ).…”

“…In comparison, Langerhans cells (LCs) in the epidermis of BP lesional skin were less likely to be associated with increased TSLP expression ( 86 ). Moreover, DC-SIGN-positive DCs, but not LCs, expressing langerin, were positive for TSLPR ( 86 ). These data suggest that keratinocytes-derived TSLP may directly activate DCs.…”

Expression of Thymic Stromal Lymphopoietin in Immune-Related Dermatoses

“…It was gradually revealed that TSLP is extensively involved in autoimmune diseases and cancers [ 3 ]. Moreover, expression of TSLP was found to participate in many inflammatory dermatoses, such as psoriasis vulgaris (PsV) [ 9 , 10 ], bullous pemphigoid (BP) [ 11 ], and alopecia areata [ 12 ]. Those diseases distinctly differ in clinical manifestations, pathology, and immune response patterns.…”