The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa
Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with a debilitating impact on quality of life. Here, we review the complex interplay of innate and adaptive immune dysregulation in HS pathogenesis, in the context of microbial dysbiosis, genetic predisposition, cell...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593253/full |
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| author | Olivia M. Burke Victoria R. Frerichs Dario F. Garcia Rivka C. Stone Rivka C. Stone Hadar Lev-Tov Hadar Lev-Tov Tali Czarnowicki Robert W. Keane Robert W. Keane Robert W. Keane Nkemcho Ojeh Nkemcho Ojeh Jelena Marjanovic Jelena Marjanovic Irena Pastar Irena Pastar Marjana Tomic-Canic Marjana Tomic-Canic Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Andrew P. Sawaya Andrew P. Sawaya |
| author_facet | Olivia M. Burke Victoria R. Frerichs Dario F. Garcia Rivka C. Stone Rivka C. Stone Hadar Lev-Tov Hadar Lev-Tov Tali Czarnowicki Robert W. Keane Robert W. Keane Robert W. Keane Nkemcho Ojeh Nkemcho Ojeh Jelena Marjanovic Jelena Marjanovic Irena Pastar Irena Pastar Marjana Tomic-Canic Marjana Tomic-Canic Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Andrew P. Sawaya Andrew P. Sawaya |
| author_sort | Olivia M. Burke |
| collection | DOAJ |
| description | Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with a debilitating impact on quality of life. Here, we review the complex interplay of innate and adaptive immune dysregulation in HS pathogenesis, in the context of microbial dysbiosis, genetic predisposition, cellular dysfunction and epigenetic factors. Hyperactivation of the innate system triggered by follicular occlusion leads to a cascade of activated signaling pathways leading to persistent inflammation as the disease progresses. This immune hyperactivation is further complicated by microbiome dysbiosis, which is associated with dysregulation of inflammasomes and altered expression of host antimicrobial peptides. Keratinocytes, fibroblasts, macrophages, and neutrophils exhibit altered functions, and contribute to the inflammatory cascade and disease chronicity in HS. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs modulate immune responses and contribute to aberrant cytokine and chemokine expression that drive the persistent inflammatory state in HS pathogenesis. We highlight the need for future research to explore the concept of epigenetic memory in epidermal stem cells and inflammasome activation to gain a better understanding of these mechanisms and pave the way for development of future novel therapeutic targets and strategies to disrupt the persistent chronic inflammation cycle in this debilitating condition. |
| format | Article |
| id | doaj-art-5a77bcdba07d4b7e91136bc4694964c9 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-5a77bcdba07d4b7e91136bc4694964c92025-08-20T03:53:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15932531593253The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativaOlivia M. Burke0Victoria R. Frerichs1Dario F. Garcia2Rivka C. Stone3Rivka C. Stone4Hadar Lev-Tov5Hadar Lev-Tov6Tali Czarnowicki7Robert W. Keane8Robert W. Keane9Robert W. Keane10Nkemcho Ojeh11Nkemcho Ojeh12Jelena Marjanovic13Jelena Marjanovic14Irena Pastar15Irena Pastar16Marjana Tomic-Canic17Marjana Tomic-Canic18Juan Pablo de Rivero Vaccari19Juan Pablo de Rivero Vaccari20Juan Pablo de Rivero Vaccari21Andrew P. Sawaya22Andrew P. Sawaya23Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDepartment of Physiology and Biophysics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDepartment of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Neurological Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesFaculty of Medical Sciences, The University of the West Indies, Cave Hill, Cave Hill, BarbadosDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesDepartment of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Physiology and Biophysics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDepartment of Neurological Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United StatesWound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miami, FL, United StatesHidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with a debilitating impact on quality of life. Here, we review the complex interplay of innate and adaptive immune dysregulation in HS pathogenesis, in the context of microbial dysbiosis, genetic predisposition, cellular dysfunction and epigenetic factors. Hyperactivation of the innate system triggered by follicular occlusion leads to a cascade of activated signaling pathways leading to persistent inflammation as the disease progresses. This immune hyperactivation is further complicated by microbiome dysbiosis, which is associated with dysregulation of inflammasomes and altered expression of host antimicrobial peptides. Keratinocytes, fibroblasts, macrophages, and neutrophils exhibit altered functions, and contribute to the inflammatory cascade and disease chronicity in HS. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs modulate immune responses and contribute to aberrant cytokine and chemokine expression that drive the persistent inflammatory state in HS pathogenesis. We highlight the need for future research to explore the concept of epigenetic memory in epidermal stem cells and inflammasome activation to gain a better understanding of these mechanisms and pave the way for development of future novel therapeutic targets and strategies to disrupt the persistent chronic inflammation cycle in this debilitating condition.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593253/fullhidradenitis suppurativainnate immunityepigeneticsinflammasomesinflammatory skin disease |
| spellingShingle | Olivia M. Burke Victoria R. Frerichs Dario F. Garcia Rivka C. Stone Rivka C. Stone Hadar Lev-Tov Hadar Lev-Tov Tali Czarnowicki Robert W. Keane Robert W. Keane Robert W. Keane Nkemcho Ojeh Nkemcho Ojeh Jelena Marjanovic Jelena Marjanovic Irena Pastar Irena Pastar Marjana Tomic-Canic Marjana Tomic-Canic Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Juan Pablo de Rivero Vaccari Andrew P. Sawaya Andrew P. Sawaya The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa Frontiers in Immunology hidradenitis suppurativa innate immunity epigenetics inflammasomes inflammatory skin disease |
| title | The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| title_full | The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| title_fullStr | The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| title_full_unstemmed | The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| title_short | The impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| title_sort | impact of innate immunity and epigenetics in the pathogenesis of hidradenitis suppurativa |
| topic | hidradenitis suppurativa innate immunity epigenetics inflammasomes inflammatory skin disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593253/full |
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