Keratinocytes – Amplifiers of Immune Responses in Systemic Lupus Erythematosus

Tsokos GC. The immunology of systemic lupus erythematosus. Nat Immunol. 2024;25(8):1332–43. https://doi.org/10.1038/s41590-024-01898-7.

Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol. 2011;12(9):565–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kortekaas Krohn I, Aerts JL, Breckpot K, Goyvaerts C, Knol E, Van Wijk F, et al. T-cell subsets in the skin and their role in inflammatory skin disorders. Allergy. 2022;77(3):827–42.

Article  CAS  PubMed  Google Scholar 

Brown SJ. Keratinocytes listen, respond, and actively contribute to Crosstalk in the Epidermal Community and Beyond. J Invest Dermatol. 2024;S0022-202X(24)01732-9. https://doi.org/10.1016/j.jid.2024.03.045.

Gallo RL. Human skin is the largest epithelial surface for Interaction with microbes. J Invest Dermatol. 2017;137(6):1213–4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang Y, Tsoi LC, Billi AC, Ward NL, Harms PW, Zeng C et al. Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin. JCI Insight. 2020;5(20).

Lai Y, Gallo RL. Toll-like receptors in skin infections and inflammatory diseases. Infect Disord Drug Targets. 2008;8(3):144–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burian M, Schmidt MF, Yazdi AS. The NLRP1 inflammasome in skin diseases. Front Immunol. 2023;14:1111611.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prochnicki T, Vasconcelos MB, Robinson KS, Mangan MSJ, De Graaf D, Shkarina K, et al. Mitochondrial damage activates the NLRP10 inflammasome. Nat Immunol. 2023;24(4):595–603.

Article  CAS  PubMed  Google Scholar 

Smatlik N, Drexler SK, Burian M, Röcken M, Yazdi AS. ASC speck formation after Inflammasome activation in primary human keratinocytes. Oxid Med Cell Longev. 2021;2021:7914829.

Article  PubMed  PubMed Central  Google Scholar 

Damm A, Giebeler N, Zamek J, Zigrino P, Kufer TA. Epidermal NLRP10 contributes to contact hypersensitivity responses in mice. Eur J Immunol. 2016;46(8):1959–69.

Article  CAS  PubMed  Google Scholar 

Fenini G, Grossi S, Contassot E, Biedermann T, Reichmann E, French LE, et al. Genome editing of human primary keratinocytes by CRISPR/Cas9 reveals an essential role of the NLRP1 inflammasome in UVB sensing. J Invest Dermatol. 2018;138(12):2644–52.

Article  CAS  PubMed  Google Scholar 

Jiao H, Wachsmuth L, Kumari S, Schwarzer R, Lin J, Eren RO, et al. Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature. 2020;580(7803):391–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Almine JF, O’Hare CA, Dunphy G, Haga IR, Naik RJ, Atrih A, et al. IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nat Commun. 2017;8:14392.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crow MK. Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets. Ann Rheum Dis. 2023;82(8):999–1014.

Article  CAS  PubMed  Google Scholar 

Sarkar MK, Hile GA, Tsoi LC, Xing X, Liu J, Liang Y, et al. Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Ann Rheum Dis. 2018;77(11):1653–64.

Article  CAS  PubMed  Google Scholar 

Stannard JN, Reed TJ, Myers E, Lowe L, Sarkar MK, Xing X, et al. Lupus skin is primed for IL-6 inflammatory responses through a keratinocyte-mediated autocrine type I Interferon Loop. J Invest Dermatol. 2017;137(1):115–22.

Article  CAS  PubMed  Google Scholar 

Billi AC, Ma F, Plazyo O, Gharaee-Kermani M, Wasikowski R, Hile GA, et al. Nonlesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation. Sci Transl Med. 2022;14(642):eabn2263.

Carter LM, Wigston Z, Laws P, Vital EM. Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers. Br J Dermatol. 2023;189(2):210–8.

Article  PubMed  Google Scholar 

Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, et al. Anifrolumab, an Anti-Interferon-α receptor monoclonal antibody, in moderate-to-severe systemic Lupus Erythematosus. Arthritis Rheumatol (Hoboken NJ). 2017;69(2):376–86.

Article  CAS  Google Scholar 

Theofilopoulos AN, Baccala R, Beutler B, Kono DH. TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITY. Annual Review of Immunology. 2005;23(Volume 23, 2005):307– 35.

Barrat FJ, Elkon KB, Fitzgerald KA. Importance of nucleic acid recognition in inflammation and autoimmunity. Annu Rev Med. 2016;67:323–36. 67, 2016.

Article  CAS  PubMed  Google Scholar 

Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol. 2021;21(9):548–69.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Skopelja-Gardner S, An J, Elkon KB. Role of the cGAS–STING pathway in systemic and organ-specific diseases. Nat Rev Nephrol. 2022;18(9):558–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015;520(7548):553–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016;22(2):146–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caielli S, Athale S, Domic B, Murat E, Chandra M, Banchereau R, et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J Exp Med. 2016;213(5):697–713.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caielli S, Cardenas J, de Jesus AA, Baisch J, Walters L, Blanck JP, et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell. 2021;184(17):4464–e7919.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berndt N, Wolf C, Fischer K, Cura Costa E, Knuschke P, Zimmermann N, et al. Photosensitivity and cGAS-Dependent IFN-1 activation in patients with Lupus and TREX1 Deficiency. J Invest Dermatology. 2022;142(3, Part A):633–e406.

Article  CAS  Google Scholar 

Lei Y, VanPortfliet JJ, Chen YF, Bryant JD, Li Y, Fails D, et al. Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity. Cell. 2023;186(14):3013–32.e22.

Xu B, Musai J, Tan YS, Hile GA, Swindell WR, Klein B et al. A critical role for IFN-β signaling for IFN-κ induction in keratinocytes. Front Lupus. 2024;2.

Goel RR, Wang X, O’Neil LJ, Nakabo S, Hasneen K, Gupta S, et al. Interferon lambda promotes immune dysregulation and tissue inflammation in TLR7-induced lupus. Proc Natl Acad Sci U S A. 2020;117(10):5409–19.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cozzani E, Drosera M, Gasparini G, Parodi A. Serology of Lupus Erythematosus: correlation between Immunopathological features and clinical aspects. Autoimmune Dis. 2014;2014:321359.

PubMed  PubMed Central  Google Scholar 

Lazzari E, Korczeniewska J, Smith JNG, Barnes S, Jefferies BJ. TRIpartite motif 21 (TRIM21) differentially regulates the stability of interferon regulatory factor 5 (IRF5) isoforms. PLoS ONE. 2014;9(8):e103609.

Article  PubMed  PubMed Central  Google Scholar 

Yang B, Wang J, Sun B. Trim21: a novel negative regulator in DNA sensor signaling. Cell Mol Immunol. 2013;10(3):190–2.

Article  CAS  PubMed  PubMed Central 

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