Abstract
Mycosis fungoides (MF) is the most common subtype of primary cutaneous T cell lymphomas, whereas pityriasis lichenoides chronica (PLC) is a chronic inflammatory skin disorder. The inflammasome is a part of the natural immune system which has a multimeric structure consisting of the receptor, adaptor and effector protein that show specificity for various ligands or activators. After the activation of the inflammasome complex, caspase 1 becomes activated which subsequently triggers interleukin-18 (IL-18) and interleukin-1β (IL-1β) production. In our study we aimed to examine the roles of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) inflammasomes in the etiopathogeneses of PLC and MF. NLRP1, NLRP3, caspase 1, IL-18 and IL-1β levels were examined and compared immunohistochemically in the skin biopsies belonging to 16 control patients; 16 PLC cases, 12 cases with stage 1 MF and 12 cases with other stages of MF (stage 2–4). In the paired comparisons of NLRP1, stage 2–4 MF group and PLC group were shown to have increased levels of NLRP1 expression compared to the control group. IL-1β was also expressed at statistically significantly higher levels in each of the stage 1 MF, stage 2–4 MF and PLC groups compared to the control group. In the paired comparisons of caspase 1 and IL-18, it was found that stage 1 MF, stage 2–4 MF and PLC groups had increased levels of expression compared to the control group. Our findings suggest that the NLRP1 inflammasome pathway might play a role in the etiopathogenesis and progression of PLC and MF.
Similar content being viewed by others
Data sharing statement
The data sets used and/or analyzed during this study are available from the corresponding author on reasonable request.
References
Cerroni L (2018) Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment. Semin Cutan Med Surg 37:2–10. https://doi.org/10.12788/j.sder.2018.002
Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S, ISCL, EORTC (2007) Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 110:1713–1722. https://doi.org/10.1182/blood-2007-03-055749
Olsen EA (2015) Evaluation, diagnosis, and staging of cutaneous lymphoma. Dermatol Clin 33:643–654. https://doi.org/10.1016/j.det.2015.06.001
Rosen ST, Radvany R, Roenigk H Jr, Terasaki PI, Bunn PA Jr (1985) Human leukocyte antigens in cutaneous T cell lymphoma. J Am Acad Dermatol 12:531–534. https://doi.org/10.1016/s0190-9622(85)70075-8
Dreno B, Celerier P, Fleischmann M, Bureau B, Litoux P (1994) Presence of Epstein-Barr virus in cutaneous lesions of mycosis fungoides and Sézary syndrome. Acta Derm Venereol 74:355–357. https://doi.org/10.2340/0001555574355357
Tuyp E, Burgoyne A, Aitchison T, MacKie R (1987) A case-control study of possible causative factors in mycosis fungoides. Arch Dermatol 23:196–200
Ravat FE, Spittle MF, Russell-Jones R (2006) Primary cutaneous T cell lymphoma occurring after organ transplantation. J Am Acad Dermatol 54:668–675. https://doi.org/10.1016/j.jaad.2005.10.015
Kim EJ, Hess S, Richardson SK, Newton S, Showe LC, Benoit BM, Ubriani R, Vittorio CC, Junkins-Hopkins JM, Wysocka M, Rook AH (2005) Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin 115:798–812. https://doi.org/10.1172/JCI24826
Bowers S, Warshaw EM (2006) Pityriasis lichenoides and its subtypes. J Am Acad Dermatol 55:557–572. https://doi.org/10.1016/j.jaad.2005.07.058
Zaaroura H, Sahar D, Bick T, Bergman R (2018) Relationship between pityriasis lichenoides and mycosis fungoides: a clinicopathological, immunohistochemical, and molecular study. Am J Dermatopathol 40:409–415. https://doi.org/10.1097/DAD.0000000000001057
Kanneganti TD (2015) The inflammasome: firing up innate immunity. Immunol Rev 265:1–5. https://doi.org/10.1111/imr.12297
Chan AH, Schroder K (2020) Inflammasome signaling and regulation of interleukin-1 family cytokines. J Exp Med 217:e20190314. https://doi.org/10.1084/jem.20190314
Sharma D, Kanneganti TD (2016) The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation. J Cell Biol 213:617–629. https://doi.org/10.1083/jcb.201602089
Zhong FL, Mamaï O, Sborgi L, Boussofara L, Hopkins R, Robinson K, Szeverényi I, Takeichi T, Balaji R, Lau A, Tye H, Roy K, Bonnard C, Ahl PJ, Jones LA, Baker PJ, Lacina L, Otsuka A, Fournie PR, Malecaze F, Lane EB, Akiyama M, Kabashima K, Connolly JE, Masters SL, Soler VJ, Omar SS, McGrath JA, Nedelcu R, Gribaa M, Denguezli M, Saad A, Hiller S, Reversade B (2016) Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell 167:187-202.e17. https://doi.org/10.1016/j.cell.2016.09.001
Eyraud A, Milpied B, Thiolat D, Darrigade AS, Boniface K, Taïeb A, Seneschal J (2018) Inflammasome activation characterizes lesional skin of folliculitis decalvans. Acta Derm Venereol 98:570–575. https://doi.org/10.2340/00015555-2924
Silva LM, de Sousa JR, Hirai KE, Dias LB Jr, Furlaneto IP, Carneiro FRO, de Souza Aarão TL, Sotto MN, Quaresma JAS (2018) The inflammasome in leprosy skin lesions: an immunohistochemical evaluation. Infect Drug Resist 11:2231–2240. https://doi.org/10.2147/IDR.S172806
Awad F, Assrawi E, Louvrier C, Jumeau C, Giurgea I, Amselem S, Karabina SA (2018) Photoaging and skin cancer: Is the inflammasome the missing link? Mech Ageing Dev 172:131–137. https://doi.org/10.1016/j.mad.2018.03.003
Ahmad I, Muneer KM, Chang ME, Nasr HM, Clay JM, Huang CC, Yusuf N (2017) Ultraviolet radiation-induced downregulation of SERCA2 mediates activation of NLRP3 inflammasome in basal cell carcinoma. Photochem Photobiol 93:1025–1033. https://doi.org/10.1111/php.12725
Marie J, Kovacs D, Pain C, Jouary T, Cota C, Vergier B, Picardo M, Taieb A, Ezzedine K, Cario-André M (2014) Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br J Dermatol 170:816–823. https://doi.org/10.1111/bjd.12691
Rathinam VA, Fitzgerald KA (2016) Inflammasome complexes: emerging mechanisms and effector functions. Cell 165:792–800. https://doi.org/10.1016/j.cell.2016.03.046
Stutz A, Golenbock DT, Latz E (2009) Inflammasomes: too big to miss. J Clin Invest 119:3502–3511. https://doi.org/10.1172/JCI40599
Yoshikawa FS, Ferreira LG, de Almeida SR (2015) IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the IL-17 response in vivo. Virulence 6:449–457. https://doi.org/10.1080/21505594.2015.1020274
Mao L, Zhang L, Li H, Chen W, Wang H, Wu S, Guo C, Lu A, Yang G, An L, Abliz P, Meng G (2014) Pathogenic fungus Microsporum canis activates the NLRP3 inflammasome. Infect Immun 82:882–892. https://doi.org/10.1128/IAI.01097-13
Liang N, Yang YP, Li W, Wu YY, Zhang ZW, Luo Y, Fan YM (2018) Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in Malassezia folliculitis. Mycoses 61:111–118. https://doi.org/10.1111/myc.12711
Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J (2019) The role of interleukin-1 in general pathology. Inflamm Regen 39:12. https://doi.org/10.1186/s41232-019-0101-5
Savvateeva MV, Savina MI, Markusheva LI, Samsonov VA (2002) Relative content of cytokines in different tissues in mycosis fungoides. Bull Exp Biol Med 134:175–176. https://doi.org/10.1023/a:1021148601424
Yamanaka K, Clark R, Dowgiert R, Hurwitz D, Shibata M, Rich BE, Hirahara K, Jones DA, Eapen S, Mizutani H, Kupper TS (2006) Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma. Clin Cancer Res 12:376–382. https://doi.org/10.1158/1078-0432.CCR-05-1777
Pileri A, Neri I, Raone B, Ciabatti S, Bellini F, Patrizi A (2012) Mycosis fungoides following pityriasis lichenoides: an exceptional event or a potential evolution. Pediatr Blood Cancer 58:306. https://doi.org/10.1002/pbc.23260
Acknowledgements
The authors gratefully thank Cem Yavrum and Rasimcan Meral for their help with statistical analysis and graphs; Ziya Birinci for performing immunohistochemical stainings and also Alper Kalyoncu for meticulous editing of the manuscript.
Funding
The present study was supported by the Turkish Society of Dermatology.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by the author(s).
Ethical committee approval
Ethical committee approval and written consent of the patients were obtained.
Informed consent
The patients in this manuscript have given written informed consent to publication of their case details.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bostan, E., Gokoz, O. & Atakan, N. The role of NLRP1 and NLRP3 inflammasomes in the etiopathogeneses of pityriasis lichenoides chronica and mycosis fungoides: an immunohistochemical study. Arch Dermatol Res 315, 231–239 (2023). https://doi.org/10.1007/s00403-022-02363-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-022-02363-x