T helper cell differentiation. T helper (TH) cells are the central organizer of adaptive immunity. Upon activation, T helper progenitors differentiate towards different functional subsets. Mis-regulation of T helper cells is involved in immune deficiency, inflammatory and autoimmune diseases, and even in cancer. In the past decade or two, numerous findings by many groups, including ours, shed light on the understanding of T helper cells in health and diseases. In addition, phenotype switch of TH cells implicates potential opportunities for targeting these cells in diseases. Our lab continues working on T helper cell differentiation, plasticity and function.
TH17 cell and its cytokines in inflammatory and autoimmune diseases. TH17 cell and its cytokines in inflammatory and autoimmune diseases. TH17 cells, a recently described T helper subset, secrete IL-17, IL-17F, IL-21, IL-22 and TNF and regulate tissue inflammation. TH17 cells have been shown to play a critical role in many inflammatory diseases. (A) Neuroinflammation. TH17 cells play an important role in experimental autoimmune encephalomyelitis, a mouse model of human multiple sclerosis. We are investigating how TH17 cells influence inflammatory infiltrates crossing the brain-blood barrier and how TH17 cells co-operate with other types of cells to cause nerve system damage. (B) Differential function of IL-17 and IL-17F. We and others have demonstrated that IL-17 and IL-17F, the two closest homologs of the IL-17 cytokine family, share pro-inflammatory features but have distinct functions when acting on various tissues. Particularly, we are interested in inflammation in the gut. Understanding the molecular basis whereby the cytokines, IL-17 and IL-17F lead to differential function is one of our current foci.
T helper cells in allergy. TH2 cells play a critical role in allergic asthma. Recently, TH9 cells were found joining in the battle. Our interests are to characterize the regulation of TH9 cell differentiation and the effector cytokine IL-9 signaling in allergic diseases.
Selected PublicationsLink to PubMed
Note: *Co-first author; #Corresponding author
Castillo EF, Zheng H, Van Cabanlong C, Dong F, Luo Y, Yang Y, Liu M, Kao WW, Yang XO#,. Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells. Eur J Immunol. 2016 Sep 29. (2016).
Zheng H, Zhang X, Castillo EF, Luo Y, Liu M, Yang XO#,. Leptin enhances TH2 and ILC2 responses in allergic airway disease. Journal of Biological Chemistry. 2016 Aug 26. (2016).
Ding X, Luo Y, Zhang X, Zheng H, Yang X, Yang X, Liu M. IL-33 driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity. J Endocrinol. 2016 Oct;231(1):35-48. (2016).
Yang XO#, Zhang H, Kim BS, Niu X, Peng J, Chen Y, Kerketta R, Lee YH, Chang SH, Corry DB, Wang D, Watowich SS, Dong C. The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation. Nature Immunology. Jun 2;14(7):732-40. (2013). PMID: 23727894
Wang X, Zhang Y, Yang XO, Nurieva RI, Chang SH, Ojeda SS, Kang HS, Schluns KS, Gui J, Jetten AM, Dong C. Transcription Il17 and Il17f is controlled by conserved noncoding sequence 2. Immunity. Jan 27;36(1):23-31 (2012). PMID: 22244845
Peng J*, Yang XO*#, Chang SH, Yang J, and Dong C.# IL-23 signaling enhances Th2 polarization and regulates allergic airway inflammation. Cell Res. 20(1): 62-71 (2010). PMID: 19935773
Yang XO#, Angkasekwinai P, Zhu J, Peng J, Liu Z, Nurieva R, Liu X, Chung Y, Chang SH, Sun B#, and Dong C.# Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment. Nat. Immunol. 10(12): 1260-1266 (2009). PMID: 19881507
Nurieva R*, Yang XO*, Chung Y*, and Dong C. Cutting edge: in vitro generated Th17 cells maintain their cytokine expression program in normal but not lymphopenic hosts. J. Immunol. 182(5): 2565-2568 (2009). PMID: 19234148
Yang XO*, Nurieva R*, Martinez GJ*, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, Feng XH, Jetten AM and Dong C. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1): 44-56 (2008). PMID: 18585065
Yang XO*, Chang SH*, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z and Dong C. Regulation of inflammatory responses by IL-17F. J. Exp. Med. 205(5): 1063-1075 (2008). PMID: 18411338
Yang XO*, Pappu BP*, Nurieva R*, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM and Dong C. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28(1): 29-39 (2008). PMID: 18164222
Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, and Dong C. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448(7152): 480-483 (2007). PMID: 17581589
Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, and Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282(13): 9358-9363 (2007). PMID: 17277312
Park H*, Li Z*, Yang XO*, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, and Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6(11): 1133-1141 (2005). PMID: 16200068