Might Necrotic Keratinocytes Contribute to the Diagnosis and Pathogenesis of Psoriasis?
Keywords:
Necrotic keratinocytes, PANoptosis, psoriasis, psoriasiform spongiotic dermatitisAbstract
Introduction: Psoriasis is a chronic inflammatory skin disease that can pose challenges in histopathological diagnosis. The diagnostic importance of necrotic keratinocytes has recently been emphasized. Necrotic keratinocytes refer to keratinocytes undergoing programmed cell death. It is increasingly evident that programmed cell death pathways play a significant role in the development and progression of psoriasis. Moreover, studies have revealed the involvement of programmed cell death mechanism called PANoptosis in the pathogenesis of psoriasis.
Objectives: In this study, our objective was to investigate the significance of necrotic keratinocytes in both the diagnosis and pathogenesis of psoriasis.
Methods: We analyzed the number of necrotic keratinocytes in 135 samples of psoriasis, 57 samples of psoriasiform spongiotic dermatitis, and 71 samples of normal skin. Additionally, we assessed the distribution of necrotic keratinocytes in the upper, middle, and lower thirds of the epidermis.
Results: Our findings showed a significant difference in the total number of necrotic keratinocytes and their distribution among the epidermal regions between patients with psoriasis and both the psoriasiform spongiotic dermatitis and control groups (p<0.001). Specifically, necrotic keratinocytes were predominantly found in the upper epidermis (77.5%) in psoriasis cases. Furthermore, we observed a strong correlation between the Psoriasis Area and Severity Index (PASI) scores and the total count of necrotic keratinocytes in psoriasis patients (r = 0.72).
Conclusions: Our study highlights the role of necrotic keratinocytes, resulting from programmed cell death, as important marker cells in both the diagnosis and pathogenesis of psoriasis.
References
Zhang Y, Xu X, Cheng H, Zhou F. AIM2 and Psoriasis. Front Immunol. 2023;14:1085448. DOI: 10.3389/fimmu.2023.1085448. PMID: 36742336.
Albanesi C, Madonna S, Gisondi P, Girolomoni G. The Interplay Between Keratinocytes and Immune Cells in the Pathogenesis of Psoriasis. Front Immunol. 2018;9:1549. DOI: 10.3389/fimmu.2018.01549. PMID: 30034395.
Duan X, Liu X, Liu N, et al. Inhibition of keratinocyte necroptosis mediated by RIPK1/RIPK3/MLKL provides a protective effect against psoriatic inflammation. Cell Death Dis. 2020;11(2):134. DOI: 10.1038/s41419-020-2328-0. PMID: 32075957.
Wang L, Zhu Y, Zhang L, et al. Mechanisms of PANoptosis and relevant small-molecule compounds for fighting diseases. Cell Death Dis. 2023;14(12):851. DOI: 10.1038/s41419-023-06370-2. PMID: 38129399.
Lu L, Zhang B, Shi M, Liu A. Identification of PANoptosis-related biomarkers and immune infiltration characteristics in psoriasis. Medicine (Baltimore). 2023;102(42):e35627. DOI: 10.1097/MD.0000000000035627. PMID: 37861483.
Gullett JM, Tweedell RE, Kanneganti TD. It's All in the PAN: Crosstalk, Plasticity, Redundancies, Switches, and Interconnectedness Encompassed by PANoptosis Underlying the Totality of Cell Death-Associated Biological Effects. Cells. 2022;11(9):1495. DOI: 10.3390/cells11091495. PMID: 35563804.
Hu XM, Zheng S, Zhang Q, et al. PANoptosis signaling enables broad immune response in psoriasis: From pathogenesis to new therapeutic strategies. Comput Struct Biotechnol J. 2023;23:64-76. DOI: 10.1016/j.csbj.2023.11.049. PMID: 38125299.
Cloutier JM, Hsi A, Camacho C, Lazova R. Necrotic Keratinocytes Are Common in Psoriasis and Have a Predilection to the Upper Epidermis: A Quantitative and Comparative Analysis. Am J Dermatopathol. 2020;42(1):20-23. DOI: 10.1097/DAD.0000000000001444. PMID: 31094719.
Kim BY, Choi JW, Kim BR, Youn SW. Histopathological findings are associated with the clinical types of psoriasis but not with the corresponding lesional psoriasis severity index. Ann Dermatol. 2015;27(1):26-31. DOI: 10.5021/ad.2015.27.1.26. PMID: 25673928.
Žurauskas M, Barkalifa R, Alex A, et al. Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin. Sci Rep. 2020;10(1):9154. DOI: 10.1038/s41598-020-65689-4. PMID: 32513976.
Wick MR. Psoriasiform dermatitides: A brief review. Semin Diagn Pathol. 2017;34(3):220-225. DOI: 10.1053/j.semdp.2016.12.006. PMID: 28094165.
Cohen JN, Bowman S, Laszik ZG, North JP. Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: A retrospective study of T helper type 2 and 17 subsets, interleukin 36, and β-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated dermatitis. J Am Acad Dermatol. 2020;82(2):430-439. DOI: 10.1016/j.jaad.2019.08.023. PMID: 31859047.
Chau T, Parsi KK, Ogawa T, et al. Psoriasis or not? Review of 51 clinically confirmed cases reveals an expanded histopathologic spectrum of psoriasis. J Cutan Pathol. 2017;44(12):1018-1026. DOI: 10.1111/cup.13033. PMID: 28833447.
Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20(6):1475. DOI: 10.3390/ijms20061475. PMID: 30909615.
Krawczyk A, Miśkiewicz J, Strzelec K, Wcisło-Dziadecka D, Strzalka-Mrozik B. Apoptosis in Autoimmunological Diseases, with Particular Consideration of Molecular Aspects of Psoriasis. Med Sci Monit. 2020;26:e922035. DOI: 10.12659/MSM.922035. PMID: 32567582.
Malireddi RKS, Kesavardhana S, Kanneganti TD. ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis). Front Cell Infect Microbiol. 2019;9:406. DOI: 10.3389/fcimb.2019.00406. PMID: 31850239.
Karki R, Sharma BR, Tuladhar S, et al. Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 2021;184(1):149-168.e17. DOI: 10.1016/j.cell.2020.11.025. PMID: 33278357.
Deng G, Chen W, Wang P, et al. Inhibition of NLRP3 inflammasome-mediated pyroptosis in macrophage by cycloastragenol contributes to amelioration of imiquimod-induced psoriasis-like skin inflammation in mice. Int Immunopharmacol. 2019;74:105682. DOI: 10.1016/j.intimp.2019.105682. PMID: 31203155.
Verma D, Fekri SZ, Sigurdardottir G, Bivik Eding C, Sandin C, Enerbäck C. Enhanced Inflammasome Activity in Patients with Psoriasis Promotes Systemic Inflammation. J Invest Dermatol. 2021;141(3):586-595.e5. DOI: 10.1016/j.jid.2020.07.012. PMID: 32896537.
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