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The following is a summary of “Inborn errors of immunity reveal the molecular requirements for the generation and maintenance of human IL-9 expressing cells.,” published in the November 2024 issue of Allergy and Immunology by Rao et al. 

CD4⁺ T cells are crucial in adaptive immunity, with various subsets contributing to host defense and immune regulation. IL-9 producing Th9 cells, identified in 2008, play both protective and pathogenic roles, but the molecular requirements for their generation are not fully understood. 

Researchers conducted a retrospective study to define the signaling pathways that regulate IL-9 production in human CD4⁺ T cells.  

They cultured human naive and memory CD4⁺ T cells under various conditions to assess IL-9 induction. They evaluated CD4⁺ T cells from 92 patients, including 21 with pathogenic variants in key immune genes, to determine their ability to differentiate into IL-9⁺ cells. 

The results showed that TGFβ plus IL-4 and a combination of IL-21, IL-23, IL-6, IL-1β, and TGFβ induced IL-9⁺ cells from naïve CD4⁺ T cells and amplified IL-9 production from memory CD4⁺ T cells. Combining these conditions synergistically generated IL-9⁺ CD4⁺ T cells. IL-9 induction required STAT3-activating cytokines, intact TCR and STAT5 signaling, and was restrained by IFNγ/STAT1 and IL-10. 

Our findings identified critical molecules that regulate IL-9 production in human CD4⁺ T cells. These pathways could be targeted to modulate IL-9 in health and disease. 

Source: jacionline.org/article/S0091-6749(24)01283-1/abstract