Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells: relevance for cutaneous lupus and vitiligo pathogenesis

Abstract

These data demonstrate that interaction between HSP70 and pDCs in CLE and vitiligo is a prerequisite for the enhancement of IFN-α production, and could be an interesting target.

Vitiligo and lupus: more similarities than meets the eye

“…In summary, the results of Jacquemin et al . are an important contribution linking previously isolated findings in vitiligo and lupus . This helps our understanding of these complex disorders and could aid the development of a targeted therapeutic approach.…”

“…In a comprehensive series of experiments, Jacquemin et al . showed that HSP70 potentiates IFN‐α production by pDCs . Additionally, they demonstrated that HSP70‐induced IFN‐α triggers the release of CXCL9 and CXCL10 by keratinocytes.…”

“…Interestingly, HSP70 represents an ideal candidate to execute a central driving role in Koebner‐induced disease. HSP70 is dramatically upregulated in lupus keratinocytes after ultraviolet B exposure . Likewise, vitiligo melanocytes secrete increased amounts of HSP70 compared with healthy melanocytes in response to cellular stress .…”

“…Jacquemin and colleagues found that in both vitiligo and lupus skin, plasmacytoid dendritic cells (pDCs) were located in proximity to HSP70‐expressing keratinocytes . This illustrates that HSP70 is likely to impact the activity of pDCs in these disorders.…”

Treatment with Modified Heat Shock Protein Repigments Vitiligo Lesions in Sinclair Swine

“…The treatment is through delivery of a DNA plasmid encoding a modified HSP70i. The rationale for this approach is based on previous work that reported induction of HSP70i in human vitiligo lesions, by stressed melanocytes, and by melanocytes exposed to vitiligo-inducing chemicals; HSP70i can also stimulate plasmacytoid dendritic cells to produce proinflammatory cytokines (Abdou et al, 2013;Jacquemin et al, 2017;Kroll et al, 2005;Mosenson et al, 2014). Mechanistic studies in mice showed that HSP70i is required for vitiligo, that its overexpression worsens vitiligo, and that a mutant HSP70i molecule (HSP70iQ435A) could prevent disease (Denman et al, 2008;Mosenson et al, 2011).…”