Abstract
Bullous pemphigoid (BP) is a cutaneous autoimmune disease, characterized by an inflammatory cascade leading to blister formation. Although macrophages were shown to participate in BP pathophysiology, their role in the blister formation process still needs to be investigated. We here addressed the influence of serum and blister fluid (BF) from patients with BP on the polarization status of macrophages with regards to the metalloproteinase-9 (MMP-9) expression. We demonstrated that several markers related to the alternatively activated macrophage phenotype (M2) including IL-10, TARC, arginase, TNFα, and IL-1RA were meaningfully increased in BF of patients with BP. We further showed that BF, but not serum from patients with BP, significantly induced the expression of CD163, CD206, and IL-10 in BP monocyte-derived macrophages (MDMs). Notably IL-10 was the only cytokine to be correlated to the reference clinical score, BP disease activity index (BPDAI), especially to the inflammatory BPDAI subscore evaluating urticarial and erythematous skin lesions (r = 0.57, p = 0.0004). We also found elevated levels of MMP-9 to M2-type macrophages ex vivo and highlighted the presence of CD163+ MMP-9+ macrophages histologically, at skin lesional site. Finally, we showed that methylprednisolone reduced MMP-9 levels in MDMs without modifying the other M2 markers. All together these results strongly support the presence of M2-phenotype macrophages with pro-inflammatory properties susceptible to favor blister formation in BP.
Highlights
Bullous pemphigoid (BP) is the most common skin autoimmune subepidermal blistering disease [1, 2]
The concentrations of TNF-α but not IFN-γ, both used as M1 type macrophage markers (Figure 1A), and of IL-10, IL-1RA, arginase used as M2 type macrophage markers (Figure 1B) showed significant increase in blister fluid (BF) compared with their concentrations in both control and BP patient sera
BF Rather Favored M2 Type Than M1 Type Macrophage Phenotype. To investigate whether those expressions were related to macrophages, we tested the effects of BF from BP patients on the expression of M1 and M2 macrophage markers by the macrophages derived from PMA-induced THP-1 monocytic cells (Figure 2)
Summary
Bullous pemphigoid (BP) is the most common skin autoimmune subepidermal blistering disease [1, 2]. The disease typically presents in the elderly with a generalized pruriginous, erythematous and bullous eruption. BP is characterized by the binding of autoantibodies directed against two components of the hemidesmosome, BP230 and BP180 that generates an inflammatory response critical for blister formation. A pathophysiological mechanism of blister formation was established, which typically involved a variety of cellular types including eosinophils, neutrophils, lymphocytes, mast cells, and macrophages [3, 4]. Mast cell activation upon immune complex binding play a major role in neutrophils recruitment, while macrophages were supposed to rather amplify the neutrophil infiltration in a mast cell-dependent fashion [5, 6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
