High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2021

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

Rui Yang
Marc Weisshaar
Federico Mele
Ibtihal Benhsaien
Jing Han
Carys Croft
Samuele Notarbartolo
Bernhard Fleckenstein
Laurie Glimcher
James Di Santo
Cindy Ma
Guy Gorochov
Aziz Bousfiha
Laurent Abel
Stuart Tangye
Jean-Laurent Casanova
Jacinta Bustamante
Federica Sallusto

Résumé

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.

Dates et versions

hal-03983907 , version 1 (11-02-2023)

Identifiants

Citer

Rui Yang, Marc Weisshaar, Federico Mele, Ibtihal Benhsaien, Karim Dorgham, et al.. High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency. Journal of Experimental Medicine, 2021, 218 (8), ⟨10.1084/jem.20202726⟩. ⟨hal-03983907⟩
8 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More