What is the role of cytokines and chemokines in the pathogenesis of bullous pemphigoid (BP)?

Updated: Oct 14, 2020
  • Author: Lawrence S Chan, MD; Chief Editor: Dirk M Elston, MD  more...
  • Print

Although no perfect active experimental model is available currently, an active animal model was generated by transferring splenocytes from wide-type mice that had been immunized by grafting human BP180-transgenic mouse skin into Rag-2(-/-)/BP180-humanized mice. [24] The recipient immunodeficient mice developed antihuman BP180 antibodies, manifested with blisters that are consistent with the clinical, histological, and immunopathological features of human bullous pemphigoid, except eosinophil infiltration. [24] In addition, the autoantibody response can be induced in healthy BALB/c mice by immunizing the mice with synthetic peptides of the mouse type XVII collagen NC16A domain, the target region of autoantibodies in human patients affected with bullous pemphigoid. [25]

Eotaxin, an eosinophil-selective chemokine, is strongly expressed in the basal layer of the epidermis of lesional bullous pemphigoid skin and parallels the accumulation of eosinophils in the skin basement membrane zone area. It may play a role in the recruitment of eosinophils to the skin basement membrane area.

Other cytokines and chemokines have also been studied in bullous pemphigoid. Interleukin 16, a major chemotactic factor responsible for recruiting CD4+ helper T cells to the skin and for inducing functional interleukin 2 receptors for cellular activation and proliferation, was found to be expressed strongly by epidermal cells and infiltrating CD4+ T cells in lesional bullous pemphigoid skin. Significantly higher levels of interleukin 16 were detected in sera and blisters of bullous pemphigoid patients compared with healthy subjects. These data (reported in 2004 and involved 39 bullous pemphigoid patients with active disease) suggest a role of interleukin 16 in bullous pemphigoid development. [26]

In other study of 27 bullous pemphigoid patients (reported in 2006), serum levels of monokine induced by interferon gamma (MIG, a Th1-type chemokine) and serum levels of CCL17 and CCL22 (Th2-type chemokines) were significantly increased in bullous pemphigoid patients compared with healthy subjects. [27]

Matrix metalloproteinase (MMP)–2, MMP-9, and MMP-13 were significantly increased in lesional bullous pemphigoid skin compared with that of healthy skin, with T cells comprising the majority of MMP cellular sources. These data (reported in 2006) suggest a role of MMP in the blistering of bullous pemphigoid. [28]

In another study of 39 bullous pemphigoid patients (reported in 2006), a cytokine named BAFF (B-cell activating factor belonging to the tumor necrosis factor family) that functions to regulate B-cell proliferation and survival was found to be significantly increased in sera of bullous pemphigoid patients compared with healthy subjects, although no significant association was noted between serum BAFF levels and titers of anti-BPAg2 antibodies. [29]

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!