Frontiers in Immunology (Feb 2021)
The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity
- Yun-Shiuan Olivia Hsu,
- Yun-Shiuan Olivia Hsu,
- Kun-Lin Lu,
- Kun-Lin Lu,
- Kun-Lin Lu,
- Kun-Lin Lu,
- Yun Fu,
- Yun Fu,
- Yun Fu,
- Yun Fu,
- Chuang-Wei Wang,
- Chuang-Wei Wang,
- Chun-Wei Lu,
- Chun-Wei Lu,
- Chun-Wei Lu,
- Chun-Wei Lu,
- Yu-Fen Lin,
- Yu-Fen Lin,
- Wen-Cheng Chang,
- Wen-Cheng Chang,
- Wen-Cheng Chang,
- Kun-Yun Yeh,
- Kun-Yun Yeh,
- Shuen-Iu Hung,
- Shuen-Iu Hung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Wen-Hung Chung,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen,
- Chun-Bing Chen
Affiliations
- Yun-Shiuan Olivia Hsu
- Department of Medical Education, Chang Gung Memorial Hospital, Linkou, Taiwan
- Yun-Shiuan Olivia Hsu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Kun-Lin Lu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Kun-Lin Lu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Kun-Lin Lu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
- Kun-Lin Lu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
- Yun Fu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Yun Fu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Yun Fu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
- Yun Fu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
- Chuang-Wei Wang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chuang-Wei Wang
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Chang Gung Immunology Consortium, Linkou, Taiwan
- Chun-Wei Lu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chun-Wei Lu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chun-Wei Lu
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
- Chun-Wei Lu
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Yu-Fen Lin
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Yu-Fen Lin
- Department of Nursing, Chang Gung Memorial Hospital, Linkou, Taiwan
- Wen-Cheng Chang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Wen-Cheng Chang
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Wen-Cheng Chang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Kun-Yun Yeh
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Kun-Yun Yeh
- 0Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
- Shuen-Iu Hung
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Shuen-Iu Hung
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Chang Gung Immunology Consortium, Linkou, Taiwan
- Wen-Hung Chung
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Wen-Hung Chung
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Wen-Hung Chung
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
- Wen-Hung Chung
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
- Wen-Hung Chung
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Chang Gung Immunology Consortium, Linkou, Taiwan
- Wen-Hung Chung
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Wen-Hung Chung
- 1Department of Dermatology, Chang Gung Hospital, Xiamen, China
- Wen-Hung Chung
- 2Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Wen-Hung Chung
- 3Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
- Wen-Hung Chung
- 4Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chun-Bing Chen
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chun-Bing Chen
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chun-Bing Chen
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
- Chun-Bing Chen
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
- Chun-Bing Chen
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Chang Gung Immunology Consortium, Linkou, Taiwan
- Chun-Bing Chen
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chun-Bing Chen
- 1Department of Dermatology, Chang Gung Hospital, Xiamen, China
- Chun-Bing Chen
- 4Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chun-Bing Chen
- 5College of Medicine, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
- DOI
- https://doi.org/10.3389/fimmu.2021.597761
- Journal volume & issue
-
Vol. 12
Abstract
The immunomodulatory effects of regulatory T cells (Tregs) and co-signaling receptors have gained much attention, as they help balance immunogenic and immunotolerant responses that may be disrupted in autoimmune and infectious diseases. Drug hypersensitivity has a myriad of manifestations, which ranges from the mild maculopapular exanthema to the severe Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS). While studies have identified high-risk human leukocyte antigen (HLA) allotypes, the presence of the HLA allotype at risk is not sufficient to elicit drug hypersensitivity. Recent studies have suggested that insufficient regulation by Tregs may play a role in severe hypersensitivity reactions. Furthermore, immune checkpoint inhibitors, such as anti-CTLA-4 or anti-PD-1, in cancer treatment also induce hypersensitivity reactions including SJS/TEN and DRESS/DIHS. Taken together, mechanisms involving both Tregs as well as coinhibitory and costimulatory receptors may be crucial in the pathogenesis of drug hypersensitivity. In this review, we summarize the currently implicated roles of co-signaling receptors and Tregs in delayed-type drug hypersensitivity in the hope of identifying potential pharmacologic targets.
Keywords
- contact dermatitis
- delayed type hypersensitivity
- drug reaction with eosinophilia and systemic symptoms
- cosignaling pathways
- immune checkpoints
- regulatory T cells
