Th9 is the newest kid of the CD4+ T-helper effector subsets to be characterised. As such, its specific role in adaptive immunity awaits clearer elucidation.
For now, its predominant role appears to be in mucosal immunity, where it bridges (innate and adaptive), augments (cell recruitment and cytokine production) and maintains (cell survival) the major effector T-helper subsets of Th17, Th2 and Th1; and even possibly down-regulates (paradoxically) through Tregs (tissue repair).
Cells driving its differentiation (through TGF-β and IL-4) are mainly innate ones like mast cells, NK cells and innate lymphoid cells. IL9 is its main mediator (also IL21), which is also produced by Th2 cells, thus the initial doubt that it was a distinct Th subset. As such, its effects most resemble Th2’s.
In health, Th9 protects against parasites and cancers (eg melanoma). It’s dysfunction is implicated in diseases like allergic asthma, ulcerative colitis and psoriasis.
One currently available inhibitor is Tofacitinib, which, through γ-chain binding, inhibits the signal transduction of IL2, 4, 7, 9, 15 & 21. Its varying success in treating the afore-mentioned conditions may be partly through the inhibition of Th9.
Human Th9 cells – Who, what and where
The Symphony of the Ninth: The development and function of Th9 cells
Th9 cells: differentiation and disease
The Development and in vivo function of TH9 cells
