Th 9 cells
Th 9 cells (T helper type 9 cells, CD4+IL-9+IL-13−IFNγ − ) are a sub-population of CD4+T cells that produce interleukin-9 (IL-9). They play a role in defense against helmint infections, in allergic responses and in autoimmunity.
Th 9 cells lack any specific biomarker and thus they are defined by their high secretion of interleukin‑9. Besides of IL-9, Th9 cells also produce IL-10 and IL-21. However, their functions in Th9 cells are still unclear.
Th9 cells can differentiate either from naive T lymphocytes or by a shift from Th2 cells. There are numbers of cytokines, transcription factors and other molecules, that have a role in Th9 differentiation.
Cytokines play a major role in development of Th9 cells. There are many cytokines impacting differentiation of Th9 cells and their production of IL-9 but IL-4 and TGF-β are indespensable for their development and polarization.
IL-4 and TGF-β are necessary for naive T lymphocytes to differentiate into Th 9 cells. while TGF-β alone can switch Th2 cells into Th9 cells.
IL-2 is critical for interleukin-9 production by Th9 cells.
IL-1 may induce IL-9 in some cases, and IL-33 is able to induce IL-9 in T cells generally. Generally IL-1 family members enhance expression of Il9 gene.
IL-25 also induces IL-9 production in vivo.
Development of Th9 cells requires a balanced cytokines signaling for its establishment. All mentioned cytokines then signal through specific transcription factors, which are later on required for a Th 9 polarization.
STAT6, IRF4, GATA3 are absolutely required for Th9 cell development and other such as PU.1, BATF, NF-κB, NFAT1, STAT5, AP-1 contribute to Th9 sub-population commitment and to IL-9 production.
STAT6 is activated by signaling through IL-4 receptor. Once activated, phosphorylated STAT6 mediate the transcription of Gata3 and Irf4, which are both necessary for polarization of Th9 cells. STAT6 repress the expression of transcription factors T-bet and Foxp3 in Th9 cells, that normally block IL-9 production.
GATA-3 in Th9 cells development represses transcriptional factor FOXP3, which would other wise let to other T helper cell subpopulation.
IRF4 binds to the promoter of Il-9 gene in Th9 cells and it is dependent on STAT6.
BATF has been also shown to bind to the Il-9 gene promoter and to activate Il-9gene transcription.
PU.1 works by directly binding to the promoter of Il-9 gene and attract chromatin-modifying enzymes which reinforce Il9-gene transcription.
NF-κB and NFAT1, are needed for a TCR-induced interleukin-9 production by Th 9 cells.
STAT5, downstream factor of IL-2, induce Th9 cells IL-9. STAT5 directly bind to Il-9 gene promoter, although it has not yet been determined how important this pathway is for Th9 development in vitro and in vivo.
...
Wikipedia