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2017 ; 198
(6
): 2302-2309
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STAT3 Activation Impairs the Stability of Th9 Cells
#MMPMID28137893
J Immunol
2017[Mar]; 198
(6
): 2302-2309
PMID28137893
show ga
Th9 cells regulate multiple immune responses, including immunity to pathogens and
tumors, allergic inflammation, and autoimmunity. Despite ongoing research into
Th9 development and function, little is known about the stability of the Th9
phenotype. In this study, we demonstrate that IL-9 production is progressively
lost in Th9 cultures during several rounds of differentiation. The loss of IL-9
is not due to an outgrowth of cells that do not secrete IL-9, as purified IL-9
secretors demonstrate the same loss of IL-9 in subsequent rounds of
differentiation. The loss of IL-9 production correlates with increases in
phospho-STAT3 levels within the cell, as well as the production of IL-10.
STAT3-deficient Th9 cells have increased IL-9 production that is maintained for
longer in culture than IL-9 in control cultures. IL-10 is responsible for STAT3
activation during the first round of differentiation, and it contributes to
instability in subsequent rounds of culture. Taken together, our results indicate
that environmental cues dictate the instability of the Th9 phenotype, and they
suggest approaches to enhance Th9 activity in beneficial immune responses.
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