Academic Journal
High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency
| العنوان: | High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency |
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| المؤلفون: | Yang, Rui, Weisshaar, Marc, Mele, Federico, Benhsaien, Ibtihal, Dorgham, Karim, Han, Jing, Croft, Carys A., Notarbartolo, Samuele, Rosain, Jérémie, Bastard, Paul, Puel, Anne, Fleckenstein, Bernhard, Glimcher, Laurie H., Di Santo, James P., Ma, Cindy S., Gorochov, Guy, Bousfiha, Aziz, Abel, Laurent, Tangye, Stuart G., Casanova, Jean-Laurent, Bustamante, Jacinta, Sallusto, Federica |
| المساهمون: | National Center for Advancing Translational Sciences, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Sackler Center for Biomedicine and Nutrition, Center for Clinical and Translational Science, Shapiro-Silverberg Fund for the Advancement of Translational Research, Rockefeller University, Immune Deficiency Foundation, Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, French National Research Agency, Fonds de Recherche en Santé Respiratoire, French Foundation for Medical Research, SCOR Corporate Foundation for Science, Swiss National Science Foundation, Institut national de la santé et de la recherche médicale, Imagine Institute, Fondation Bettencourt Schueller, Department of Health of the New South Wales Government of Australia, National Health and Medical Research Council of Australia, Stony Wold-Herbert Fund, Helmut Horten Foundation |
| المصدر: | Journal of Experimental Medicine ; volume 218, issue 8 ; ISSN 0022-1007 1540-9538 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2021 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20202726 |
| DOI: | 10.1084/jem.20202726/1823380/jem_20202726.pdf |
| الاتاحة: | http://dx.doi.org/10.1084/jem.20202726 https://rupress.org/jem/article-pdf/doi/10.1084/jem.20202726/1823380/jem_20202726.pdf |
| Rights: | http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.BE61E38 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20202726 |
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