The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity

Yun Shiuan Olivia Hsu, Kun Lin Lu, Yun Fu, Chuang Wei Wang, Chun Wei Lu, Yu Fen Lin, Wen Cheng Chang, Kun Yun Yeh, Shuen Iu Hung, Wen Hung Chung, Chun Bing Chen

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)597761
Number of pages1
JournalFrontiers in Immunology
StatePublished - 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2021 Hsu, Lu, Fu, Wang, Lu, Lin, Chang, Yeh, Hung, Chung and Chen.


  • Stevens-Johnson Syndrome
  • contact dermatitis
  • cosignaling pathways
  • delayed type hypersensitivity
  • drug reaction with eosinophilia and systemic symptoms
  • immune checkpoints
  • regulatory T cells
  • toxic epidermal necrolysis


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