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© Timothy Wai
Publication : The Journal of experimental medicine

High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of experimental medicine - 02 Aug 2021

Yang R, Weisshaar M, Mele F, Benhsaien I, Dorgham K, Han J, Croft CA, Notarbartolo S, Rosain J, Bastard P, Puel A, Fleckenstein B, Glimcher LH, Di Santo JP, Ma CS, Gorochov G, Bousfiha A, Abel L, Tangye SG, Casanova JL, Bustamante J, Sallusto F,

Link to Pubmed [PMID] – 34160550

Link to DOI – e2020272610.1084/jem.20202726

J Exp Med 2021 Aug; 218(8):

We have described a child suffering from Mendelian susceptibility to mycobacterial disease (MSMD) due to autosomal recessive, complete T-bet deficiency, which impairs IFN-γ production by innate and innate-like adaptive, but not mycobacterial-reactive purely adaptive, lymphocytes. Here, we explore the persistent upper airway inflammation (UAI) and blood eosinophilia of this patient. Unlike wild-type (WT) T-bet, the mutant form of T-bet from this patient did not inhibit the production of Th2 cytokines, including IL-4, IL-5, IL-9, and IL-13, when overexpressed in T helper 2 (Th2) cells. Moreover, Herpesvirus saimiri-immortalized T cells from the patient produced abnormally large amounts of Th2 cytokines, and the patient had markedly high plasma IL-5 and IL-13 concentrations. Finally, the patient’s CD4+ αβ T cells produced most of the Th2 cytokines in response to chronic stimulation, regardless of their antigen specificities, a phenotype reversed by the expression of WT T-bet. T-bet deficiency thus underlies the excessive production of Th2 cytokines, particularly IL-5 and IL-13, by CD4+ αβ T cells, causing blood eosinophilia and UAI. The MSMD of this patient results from defective IFN-γ production by innate and innate-like adaptive lymphocytes, whereas the UAI and eosinophilia result from excessive Th2 cytokine production by adaptive CD4+ αβ T lymphocytes.

https://pubmed.ncbi.nlm.nih.gov/34160550