TNF receptor signalling in autoinflammatory diseases

Heledd H Jarosz-Griffiths, Jonathan Holbrook, Samuel Lara-Reyna, Michael F McDermott

Research output: Contribution to journalReview articlepeer-review


Autoinflammatory syndromes are a group of disorders characterized by recurring episodes of inflammation as a result of specific defects in the innate immune system. Patients with autoinflammatory disease present with recurrent outbreaks of chronic systemic inflammation that are mediated by innate immune cells, for the most part. A number of these diseases arise from defects in the tumour necrosis factor receptor (TNFR) signalling pathway leading to elevated levels of inflammatory cytokines. Elucidation of the molecular mechanisms of these recently defined autoinflammatory diseases has led to a greater understanding of the mechanisms of action of key molecules involved in TNFR signalling, particularly those involved in ubiquitination, as found in haploinsufficiency of A20 (HA20), otulipenia/OTULIN-related autoinflammatory syndrome (ORAS) and linear ubiquitin chain assembly complex (LUBAC) deficiency. In this review, we also address other TNFR signalling disorders such as TNFR-associated periodic syndrome (TRAPS), RELA haploinsufficiency, RIPK1-associated immunodeficiency and autoinflammation, X-linked ectodermal dysplasia and immunodeficiency (X-EDA-ID) and we review the most recent advances surrounding these diseases and therapeutic approaches currently used to target these diseases. Finally, we explore therapeutic advances in TNF-related immune-based therapies and explore new approaches to target disease-specific modulation of autoinflammatory diseases.

Original languageEnglish
Pages (from-to)639-648
Number of pages10
JournalInternational Immunology
Issue number10
Publication statusPublished - 18 Sept 2019

Bibliographical note

© The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: [email protected].


  • Animals
  • Autoimmune Diseases/genetics
  • Humans
  • Inflammation/genetics
  • Receptors, Tumor Necrosis Factor/immunology
  • Signal Transduction/immunology


Dive into the research topics of 'TNF receptor signalling in autoinflammatory diseases'. Together they form a unique fingerprint.

Cite this