Research Focus：
The immune system is the defense system in humans and animals that helps fight off invading pathogens and clear tumor cells from the body. The immune system of higher animals is divided into a natural immune system and an adaptive immune system. As the name suggests, innate immunity is innate, evolutionarily conserved, and originates in lower organisms. Innate immunity provides the body's first line of defense against pathogen invasion and can quickly resist most pathogens, but it does not provide a long-term immune response and cannot specifically target specific pathogens. The adaptive immune system is unique to vertebrates and completes development after birth; And only works when the host is stimulated by antigens.
According to the different cell types involved in the immune response and their effector mechanisms, adaptive immunity can be divided into T cell-mediated cellular immune response and B-cell-mediated humoral immune response. The germinal center (GC) response is the most important physiological process in the humoral immune response. Only through germinal center selection can B cells activated by specific antigens develop and differentiate into long-acting memory B cells and plasma cells secreting long-acting, high-affinity antibodies. This germinal center selection process is controlled by Follicular helper T cells (TFH). Therefore, the molecular mechanism by which TFH helps B cell differentiation is the theoretical basis for all vaccine development.
Bcl-6 is a key transcription factor guiding TFH differentiation, and the inducible costimulant receptor ICOS is also critical for TFH differentiation, which is able to induce Bcl-6 expression through the PI3K-Akt signaling pathway. Our study found that the transcription factor Foxo1 may block TFH differentiation by inhibiting the expression of Bcl-6, and further studies have shown that phosphorylation of Foxo1 by the ICOS-PI3K-Akt signaling pathway requires the ubiquitin ligase Itch to ubiquitinate Foxo1 and lead to its degradation, thereby promoting TFH differentiation. Our findings reveal the important roles of the ubiquitin ligase Itch and transcription factor Foxo1 in TFH differentiation. We will continue to study the regulatory mechanism of TFH differentiation around how Bcl-6 is induced by cell-cell contact signaling, cell metabolism and other signaling pathways. We mainly use various genetically modified mice to construct some mouse immune disease models (bacterial, viral infection, etc.) to study the function of target genes in the immune system, especially in TFH differentiation, and to study their molecular mechanisms and signaling pathways through cell models.
Educational background:
July 2000: Graduated from the College of Life Sciences, Beijing Normal University with a bachelor's degree in science.
January 2006: Ph.D., School of Life Sciences, Peking University in January 2006
Work experience:
August 2006 - April 2009: Postdoctoral research at Scripps Research Institute, USA.
May 2009 -May 2010: Postdoctoral research at Cleveland Clinic in the United States.
June 2010 -September 2014: Postdoctoral research at the La Jolla Institute of Allergy and Immunology.
December 2014 to present: Professor at the School of Life Sciences, Xiamen University, and has been selected as a high-level innovative talent in Fujian Province.
Selected Publications
1. Chen R, Bélanger S, Frederick MA, Li B, Johnston RJ, Xiao N, Liu YC, Sharma S, Peters B, Rao A, Crotty S#, Pipkin ME#. In vivo RNA interference screens identify regulators of antiviral CD4(+) and CD8(+) T cell differentiation.Immunity. 2014 Aug 21;41(2):325-38.
2. Sabouri AH, Marcondes MC, Flynn C, Berger M, Xiao N, Fox HS, Sarvetnick NE#. TLR signaling controls lethal encephalitis in WNV-infected brain.Brain Res. 2014 Jul 29;1574:84-95.
3. Xiao N, Eto D, Elly C, Peng G, Crotty S#,Liu YC#. The E3 ubiquitin ligase Itch is required for the differentiation of T follicular helper cells. Nat Immunol. 2014 Jul;15(7):657-66.
4. Yu M, Zhou H, Zhao J, Xiao N, Roychowdhury S, Schmitt D, Hu B, Harding CV, Hise AG, Hazen SL, Defranco AL, Fox PL, Morton RE, Dicorleto PE, Febbraio M, Nagy LE, Smith JD, Wang JA, Li X#. MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases. J Exp Med. 2014 May 5; 211(5):887-907.
5. Burkart C, Arimoto KI, Tang T, Cong X, Xiao N, Liu YC, Kotenko SV, Ellies LG, Zhang DE#. Usp18 deficient mammary epithelial cells create an antitumour environment driven by hypersensitivity to IFN-λ and elevated secretion of Cxcl10. EMBO Mol Med. 2013 Jul;5(7):967-82.
6. Arnold CN, Barnes MJ, Berger M, Blasius AL, Brandl K, Croker B, Crozat K, Du X, Eidenschenk C, Georgel P, Hoebe K, Huang H, Jiang Z, Krebs P, La Vine D, Li X, Lyon S, Moresco EM, Murray AR, Popkin DL, Rutschmann S, Siggs OM, Smart NG, Sun L, Tabeta K, Tomisato W, Webster V, Won S, Xia Y, Xiao N, Beutler B#. ENU-induced phenovariance in mice: inferences from 587 mutations. BMC Res Notes. 2012 Oct 24;5(1):577.
7. Cui W, Xiao N, Xiao H, Zhou H, Yu M, Gu J, Li X#. β-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-κB Activation.Mol Cell Biol. 2012 Oct;32(19):3990-4000.
8. Siggs OM*, Xiao N*, Wang Y, Shi H, Tomisato W, Li X, Xia Y, Beutler B#. iRhom2 is required for the secretion of mouse TNFα. Blood. 2012 Jun 14;119(24):5769-71.
9. Xiao N, Eidenschenk C, Krebs P, Brandl K, Blasius AL, Xia Y, Khovananth K, Smart NG, Beutler B#. The Tpl2 mutation sluggish impairs type I IFN production and increases susceptibility to group B streptococcal disease.J Immunol. 2009 Dec 15;183(12):7975-83.
10. Jimenez-Dalmaroni MJ, Xiao N, Corper AL, Verdino P, Ainge GD, Larsen DS, Painter GF, Rudd PM, Dwek RA, Hoebe K#, Beutler B#, Wilson IA#. Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts as a co-receptor for TLR2.PLoS One. 2009 Oct 22;4(10):e7411.
11. Brandl K, Rutschmann S, Li X, Du X, Xiao N, Schnabl B, Brenner DA, Beutler B#.Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response.ProcNatlAcadSci U S A. 2009 Mar 3;106(9):3300-5.
12. Xu L*, Xiao N*, Liu F, Ren H, Gu J#. Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria.ProcNatlAcadSci U S A. 2009 Feb 3;106(5):1530-5.
