Abstract
IFNs are well known as mediators of the antimicrobial response but also serve as important immunomodulatory cytokines in autoimmune and autoinflammatory diseases. An increasingly critical role for IFNs in evolution of skin inflammation in these patients has been recognized. IFNs are produced not only by infiltrating immune but also resident skin cells, with increased baseline IFN production priming for inflammatory cell activation, immune response amplification, and development of skin lesions. The IFN response differs by cell type and host factors and may be modified by other inflammatory pathway activation specific to individual diseases, leading to differing clinical phenotypes. Understanding the contribution of IFNs to skin and systemic disease pathogenesis is key to development of new therapeutics and improved patient outcomes. In this review, we summarize the immunomodulatory role of IFNs in skin, with a focus on type I, and provide insight into IFN dysregulation in autoimmune and autoinflammatory diseases.
Footnotes
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health Award R01-AR071384 (to J.M.K.), the A. Alfred Taubman Medical Research Institute (to J.M.K.), the Parfet Emerging Scholar Award (to J.M.K.), the Rheumatology Research Foundation (to J.M.K.), and the Doris Duke Charitable Foundation through a Physician Scientist Development award (to J.M.K.). J.L.T. was supported by a Eunice Kennedy Shriver National Institute of Child Health and Human Development K12 Child Health Research Center Career Development Award (K12 HD028820-28), a Michigan Institute for Clinical and Health Research Pathway to First Grant Award, and a Cure JM Foundation Research Grant. J.M.K. has received grant support from Celgene/Bristol Myers Squibb and Q32 Bio.
Abbreviations used in this article:
- AGS
- Aicardi–Goutières syndrome
- CANDLE
- chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature
- cGAS
- cyclic GMP–AMP synthase
- CLASI
- Cutaneous Lupus Erythematosus Disease Area and Severity Index
- CLE
- cutaneous lupus erythematosus
- DAMP
- damage-associated molecular pattern
- DM
- dermatomyositis
- IFNAR
- IFN-α/βR
- IRF
- IFN regulatory factor
- ISG
- IFN-stimulated gene
- JDM
- juvenile DM
- LSc
- localized scleroderma
- MxA
- myxovirus resistance gene A
- PAMP
- pathogen-associated molecular pattern
- pDC
- plasmacytoid dendritic cell
- poly(I:C)
- polyinosinic–polycytidylic acid
- PRR
- pattern recognition receptor
- SAVI
- STING-associated vasculopathy with onset in infancy
- SLE
- systemic lupus erythematosus
- SS
- Sjögren syndrome
- SSc
- systemic sclerosis
- STING
- stimulator of IFN genes
- TYK2
- tyrosine kinase 2.
- Received May 21, 2020.
- Accepted August 18, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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