Research Description
Our research will focus on two directions: (1) T 球友(中国)qys responses in mucosal surface and chronic inflammation; and (2) Identification of Type II innate sensing mechanisms.
The mucosal surface of Gastrointestinal (GI) tract is one of the major sites of immunological challenge to host immune system. The host must be able to mount protective immune responses against invading pathogenic micro-organisms while, at the same time specifically not activating these mechanisms in response to dietary antigens or the beneficial commensal flora. At steady states, gut Th17 球友(中国)qys are co-exist in a well regulated balance with Foxp3+ Treg 球友(中国)qys. Mechanisms underlying this homeostasis still remain elusive.
Chronic inflammation plays a central role in some of the most challenging diseases, including rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type I diabetes, asthma, and even neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s. The strong association between specific alleles encoded within the MHC class II region and the development of autoimmune diseases indicate that CD4+ T 球友(中国)qys are involved in the pathogenesis. The immune system needs to reach equilibrium that permits protective responses against pathogens while limits potential harmful responses targeting the “self” and provoking autoimmunity. How this balance is achieved through the interactions of different classes of T 球友(中国)qys that have pro- or anti-inflammatory activity remains to be further explored.
We are employing Immune repertoire profiling and TCR transgenic strategies to study the role of distinct T 球友(中国)qy subsets in the maintenance of gut homeostasis and the pathogenesis of chronic inflammation.
The immune system has tailored its effector functions to precisely respond to distinct microorganism species. Based on the different effector functions and involvement of T-helper 球友(中国)qy and innate lymphoid 球友(中国)qy (ILC) subsets, the innate and adaptive immune systems converge into three major kinds of effector immunity, which are usually categorized as type I, type II, and type II. During the past twenty years, the field of immunology has witnessed tremendous breakthroughs in how effector immune responses are instructed by the innate immune system. Several classes of pattern-recognition receptors (PRRs) have been identified and characterized in detail. However, the physiological roles of these PRRs are limited to the sensing of bacterial, virus and fungus colonization and instruction of type I and type III effector responses. How the innate sensing system recognizes worm infection and allergy, and consequently induces type II response remains largely unknown. Our lab will work on the sentinels of type II immune stimuli and characterize mechanisms of their recognition. The potential discoveries of this research will open up new avenues for understanding how innate immune recognitions induce distinct types of effector responses, and provide knowledge for developing novel therapies of allergic diseases such as asthma.
代表文章 Representative Publications
1. Xu M*, Pokrovskii M*, Ding Y, Yi R, Au C, Harrison OJ, Galan C, Belkaid Y, Bonneau R, Littman DR. c-Maf-dependent regulatory T 球友(中国)qys mediate immunological tolerance to intestinal microbiota. Nature. 2018 Feb 15; 554(7692):373-377. PMCID: PMC5814346 (*Equal contribution, highlighted by Nature Review of Immunology)
2. Yang Y, Torchinsky MB, Gobert M, Xiong H, Xu M, Linehan JL, Alonzo F, Ng C, Chen A, Lin X, Sczesnak A, Liao JJ, Torres VJ, Jenkins MK, Lafaille JJ, Littman DR. Focused specificity of intestinal TH17 球友(中国)qys towards commensal bacterial antigens. Nature. 2014 Jun 5;510(7503):152-6.
3. Huang C, Zhang Z, Xu M, Li Y, Li Z, Ma Y, Cai T, Zhu B. H3.3-H4 tetramer splitting events feature 球友(中国)qy-type specific enhancers. PLoS Genet. 2013 Jun;9(6):e1003558.
4. Yuan W, Wu T, Fu H, Dai C, Wu H, Liu N, Li X, Xu M, Zhang Z, Niu T, Han Z, Chai J, Zhou XJ, Gao S, Zhu B. Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science. 2012 Aug 24;337(6097):971-5.
5. Xu M, Wang W, Chen S#, Zhu B#. A model for mitotic inheritance of histone lysine methylation. EMBO Rep. 2011 Dec 23; 13(1):60-7. (#Co-correspondence)
6. Jing B, Xu S, Xu M, Li Y, Li S, Ding J, Zhang Y. Brush and spray: a high-throughput systemic acquired resistance assay suitable for large-scale genetic screening. Plant Physiol. 2011 Nov; 157(3):973-80.
7. Yuan W*, Xu M*, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem. 2011 Mar 11; 286 (10): 7983-9. (*Equal contribution)
8. Chen X, Xiong J, Xu M, Chen S, Zhu B. Symmetrical modification within a nucleosome is not required globally for histone lysine methylation. EMBO Rep. 2011 Mar; 12(3): 244-51.
9. Xu M*, Long C*, Chen X, Huang C, Chen S#, Zhu B#. Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. Science. 2010 Apr 2; 328(5974): 94-8. (*Equal contribution; #Co-correspondence)
10. Jia G, Wang W, Li H, Mao Z, Cai G, Sun J, Wu H, Xu M, Yang P, Yuan W, Chen S, Zhu B. A systematic evaluation of the compatibility of histones containing methyl-lysine analogues with biochemical reactions. 球友(中国)qy Res. 2009 Oct; 19(10):1217-20.
Review
1. Huang C, Xu M, Zhu B. Epigenetic inheritance mediated by histone lysine methylation: maintaining transcriptional states without the precise restoration of marks? Philos Trans R Soc Lond B Biol Sci. 2013 Jan 5;368(1609):20110332.
2. Xu M, Zhu B. Nucleosome assembly and epigenetic inheritance. Protein 球友(中国)qy. 2010 Sep; 1(9):820-9.
Book Chapter
1. Xu M, Chen S#, Zhu B#. Investigating the 球友(中国)qy cycle-associated dynamics of histone modifications using quantitative mass spectrometry. Methods Enzymol. 2012;512:29-55. (#Co-correspondence)
