High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency
| Autor: | Yang, Rui, Mele, Federico, Weisshaar, Marc, Sallusto, Federica |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Zdroj: | Journal of Experimental Medicine, 218 (8) |
| ISSN: | 0022-1007 1540-0069 1540-9538 |
| Popis: | 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. Journal of Experimental Medicine, 218 (8) ISSN:0022-1007 ISSN:1540-0069 ISSN:1540-9538 |
| Databáze: | OpenAIRE |
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