» Articles » PMID: 27896635

Discovery and Initial Characterization of Th9 Cells: the Early Years

Overview
Publisher Springer
Date 2016 Nov 30
PMID 27896635
Citations 10
Authors
Affiliations
Soon will be listed here.
Abstract

The launch of the Th1/Th2 concept represented a decisive breakthrough concerning our understanding of how very diverse immune reactions can be regulated by functionally different T helper subpopulations via the secretion of different panels of cytokines. In this context, IL-9 was identified to be produced by T helper cell lines in addition to Th2 cytokines IL-4 and IL-5. Detailed analyses revealed that IL-9 production of mouse CD4 T helper cells was dependent on a combination of IL-2, IL-4, and TGF-β. Roughly a decade later, it was found that TGF-β can also induce the development of CD4 Treg cells. This finding engendered a series of studies on the central role of TGF-β for cytokine-mediated T helper cell differentiation which elucidated that IL-4 curbed the Treg cell-promoting effect of TGF-β while TGF-β impaired the Th2-promoting capacity of IL-4. Instead, TGF-β in combination with IL-4 induced the development of CD4 T helper cells that preferentially produced IL-9 and that were different from Th2 cells which originally were thought to be the main source of IL-9. In addition, adoptive transfer of such IL-9-producing CD4 T helper cells was shown to cause the development of colitis and peripheral neuritis. Hence, the unique cytokine expression pattern in combination with the inflammatory in vivo phenotype led to the designation of Th9 cells as a new CD4 T helper subpopulation.

Citing Articles

CD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease.

Gomez-Bris R, Saez A, Herrero-Fernandez B, Rius C, Sanchez-Martinez H, Gonzalez-Granado J Int J Mol Sci. 2023; 24(3).

PMID: 36769019 PMC: 9916759. DOI: 10.3390/ijms24032696.


The kinase p38α functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation.

Han M, Ma J, Ouyang S, Wang Y, Zheng T, Lu P Cell Mol Immunol. 2022; 19(7):805-819.

PMID: 35551270 PMC: 9243149. DOI: 10.1038/s41423-022-00873-2.


Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression.

Zhao C, Wang D, Wu M, Luo Y, Yang M, Guo J J Int Med Res. 2020; 48(6):300060520926011.

PMID: 32567429 PMC: 7309405. DOI: 10.1177/0300060520926011.


Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD.

Tindemans I, Joosse M, Samsom J Cells. 2020; 9(1).

PMID: 31906479 PMC: 7016883. DOI: 10.3390/cells9010110.


An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis.

Chakraborty S, Kubatzky K, Mitra D Int J Mol Sci. 2019; 20(9).

PMID: 31035677 PMC: 6522352. DOI: 10.3390/ijms20092113.


References
1.
Hultner L, Druez C, Moeller J, Uyttenhove C, Schmitt E, Rude E . Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9). Eur J Immunol. 1990; 20(6):1413-6. DOI: 10.1002/eji.1830200632. View

2.
Van Snick J, Goethals A, Renauld J, Van Roost E, Uyttenhove C, Rubira M . Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J Exp Med. 1989; 169(1):363-8. PMC: 2189178. DOI: 10.1084/jem.169.1.363. View

3.
Uyttenhove C, Simpson R, Van Snick J . Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci U S A. 1988; 85(18):6934-8. PMC: 282093. DOI: 10.1073/pnas.85.18.6934. View

4.
Chang H, Sehra S, Goswami R, Yao W, Yu Q, Stritesky G . The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol. 2010; 11(6):527-34. PMC: 3136246. DOI: 10.1038/ni.1867. View

5.
Schmitt E, Beuscher H, Huels C, Monteyne P, van Brandwijk R, Van Snick J . IL-1 serves as a secondary signal for IL-9 expression. J Immunol. 1991; 147(11):3848-54. View