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Cited by 53Multiple Sclerosis Research StudiesProtein Kinase Regulation and GTPase SignalingChemokine receptors and signaling

LRCH1 interferes with DOCK8-Cdc42–induced T cell migration and ameliorates experimental autoimmune encephalomyelitis

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Xu, Xiaoyan, Han, Lei, Zhao, Guixian, Xue, Shengjie, Gao, Yunzhen, Xiao, Jun, Zhang, Shicheng, Chen, Peng +5 more·2017·Journal of Experimental Medicine
DOI 10.1084/jem.20160068PMC PMC5206493
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Abstract

Directional autoreactive CD4+ T cell migration into the central nervous system plays a critical role in multiple sclerosis. Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. Little is known about whether DOCK8 is related to multiple sclerosis (MS) and how to restrict its GEF activity. Using two screening systems, we found that LRCH1 competes with Cdc42 for interaction with DOCK8 and restrains T cell migration. In response to chemokine stimulation, PKCα phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration. Point mutations at the DOCK8 serine sites block chemokine- and PKCα-induced T cell migration. Importantly, Dock8 mutant mice or Lrch1 transgenic mice were protected from MOG (35–55) peptide–induced experimental autoimmune encephalomyelitis (EAE), whereas Lrch1-deficient mice displayed a more severe phenotype. Notably, DOCK8 expression was markedly increased in PBMCs from the acute phase of MS patients. Together, our study demonstrates LRCH1 as a novel effector to restrain PKCα–DOCK8–Cdc42 module–induced T cell migration and ameliorate EAE.

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  • DOCK8 deficiency in the brain leads to impaired activity of T-cells and microglia.

    “In the brain, DOCK8 deficiency leads to impaired activity of T-cells and microglia, with studies showing that impaired GEF activity results in ameliorated outcomes of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS) (118, 119).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [119]

    The Results sections on murine EAE and CD4+ T-cell migration report that a Dock8 mutation abolishing GEF activity reduced T-cell migration into the CNS and ameliorated EAE. They do not report impaired microglial activity, and the observed T-cell impairment is specifically in migration rather than activity generally. Page numbers are not provided in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Impaired GEF activity results in ameliorated outcomes of experimental autoimmune encephalomyelitis (EAE).

    “In the brain, DOCK8 deficiency leads to impaired activity of T-cells and microglia, with studies showing that impaired GEF activity results in ameliorated outcomes of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS) (118, 119).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [119]

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Research works printed but not linked: 64

  1. Abram C.L., and Lowell C.A. 2009 The ins and outs of leukocyte integrin signaling. Annu. Rev. Immunol. 27: 339– 362. 10.1146/annurev.immunol.021908.132554 19302044 PMC3248397 · DOI
  2. Barton A., Woolmore J.A., Ward D., Eyre S., Hinks A., Ollier W.E., Strange R.C., Fryer A.A., John S., Hawkins C.P., and Worthington J. 2004 Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population. Brain. 127: 1717– 1722. 10.1093/brain/awh193 15155525 · DOI
  3. Benard V., Bohl B.P., and Bokoch G.M. 1999 Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J. Biol. Chem. 274: 13198– 13204. 10.1074/jbc.274.19.13198 10224076 · DOI
  4. Chun J., and Hartung H.P. 2010 Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin. Neuropharmacol. 33: 91– 101. 10.1097/WNF.0b013e3181cbf825 20061941 PMC2859693 · DOI · Paper page
  5. Côté J.F., Motoyama A.B., Bush J.A., and Vuori K. 2005 A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling. Nat. Cell Biol. 7: 797– 807. 10.1038/ncb1280 16025104 PMC1352170 · DOI
  6. Damotte V., Guillot-Noel L., Patsopoulos N.A., Madireddy L., El Behi M., De Jager P.L., Baranzini S.E., Cournu-Rebeix I., Fontaine B. International Multiple Sclerosis Genetics Consortium. Wellcome Trust Case Control Consortium 2 2014 A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility. Genes Immun. 15: 126– 132. 10.1038/gene.2013.70 24430173 · DOI
  7. De Jager P.L., and Hafler D.A. 2007 New therapeutic approaches for multiple sclerosis. Annu. Rev. Med. 58: 417– 432. 10.1146/annurev.med.58.071105.111552 17217332 · DOI
  8. De Jager P.L., Jia X., Wang J., de Bakker P.I., Ottoboni L., Aggarwal N.T., Piccio L., Raychaudhuri S., Tran D., Aubin C., International MS Genetics Consortium 2009 Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat. Genet. 41: 776– 782. 10.1038/ng.401 19525953 PMC2757648 · DOI · Paper page
  9. dos Santos A.C., Barsante M.M., Arantes R.M., Bernard C.C., Teixeira M.M., and Carvalho-Tavares J. 2005 CCL2 and CCL5 mediate leukocyte adhesion in experimental autoimmune encephalomyelitis--an intravital microscopy study. J. Neuroimmunol. 162: 122– 129. 10.1016/j.jneuroim.2005.01.020 15833367 · DOI
  10. Engelhardt B., and Ransohoff R.M. 2005 The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 26: 485– 495. 10.1016/j.it.2005.07.004 16039904 · DOI
  11. Engelmann S., Togni M., Thielitz A., Reichardt P., Kliche S., Reinhold D., Schraven B., and Reinhold A. 2013 T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice. J. Immunol. 191: 4950– 4959. 10.4049/jimmunol.1203340 24101551 · DOI
  12. Etienne-Manneville S. 2004 Cdc42--the centre of polarity. J. Cell Sci. 117: 1291– 1300. 10.1242/jcs.01115 15020669 · DOI
  13. Foussard H., Ferrer P., Valenti P., Polesello C., Carreno S., and Payre F. 2010 LRCH proteins: a novel family of cytoskeletal regulators. PLoS One. 5: e12257 10.1371/journal.pone.0012257 20805893 PMC2923620 · DOI
  14. García-Mata R., Wennerberg K., Arthur W.T., Noren N.K., Ellerbroek S.M., and Burridge K. 2006 Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 406: 425– 437. 10.1016/S0076-6879(06)06031-9 16472675 · DOI
  15. Griggs B.L., Ladd S., Saul R.A., DuPont B.R., and Srivastava A.K. 2008 Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities. Genomics. 91: 195– 202. 10.1016/j.ygeno.2007.10.011 18060736 PMC2245991 · DOI
  16. Haddad E., Zugaza J.L., Louache F., Debili N., Crouin C., Schwarz K., Fischer A., Vainchenker W., and Bertoglio J. 2001 The interaction between Cdc42 and WASP is required for SDF-1-induced T-lymphocyte chemotaxis. Blood. 97: 33– 38. 10.1182/blood.V97.1.33 11133739 · DOI
  17. Han J., Lim C.J., Watanabe N., Soriani A., Ratnikov B., Calderwood D.A., Puzon-McLaughlin W., Lafuente E.M., Boussiotis V.A., Shattil S.J., and Ginsberg M.H. 2006 Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3. Curr. Biol. 16: 1796– 1806. 10.1016/j.cub.2006.08.035 16979556 · DOI
  18. Harada Y., Tanaka Y., Terasawa M., Pieczyk M., Habiro K., Katakai T., Hanawa-Suetsugu K., Kukimoto-Niino M., Nishizaki T., Shirouzu M., 2012 DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses. Blood. 119: 4451– 4461. 10.1182/blood-2012-01-407098 22461490 PMC3418773 · DOI · Paper page
  19. Itoh R.E., Kurokawa K., Ohba Y., Yoshizaki H., Mochizuki N., and Matsuda M. 2002 Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol. Cell. Biol. 22: 6582– 6591. 10.1128/MCB.22.18.6582-6591.2002 12192056 PMC135619 · DOI
  20. Jabara H.H., McDonald D.R., Janssen E., Massaad M.J., Ramesh N., Borzutzky A., Rauter I., Benson H., Schneider L., Baxi S., 2012 DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation. Nat. Immunol. 13: 612– 620. 10.1038/ni.2305 22581261 PMC3362684 · DOI
  21. Jiang Q., Shi D., Nakajima M., Dai J., Wei J., Malizos K.N., Qin J., Miyamoto Y., Kamatani N., Liu B., 2008 Lack of association of single nucleotide polymorphism in LRCH1 with knee osteoarthritis susceptibility. J. Hum. Genet. 53: 42– 47. 10.1007/s10038-007-0216-4 18049793 · DOI
  22. Jin W., Zhou X.F., Yu J., Cheng X., and Sun S.C. 2009 Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK. Blood. 113: 6603– 6610. 10.1182/blood-2008-12-192914 19411637 PMC2710918 · DOI
  23. Jo E.K., Wang H., and Rudd C.E. 2005 An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R. J. Exp. Med. 201: 1733– 1739. 10.1084/jem.20042577 15939789 PMC2213273 · DOI
  24. Katagiri K., Imamura M., and Kinashi T. 2006 Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nat. Immunol. 7: 919– 928. 10.1038/ni1374 16892067 · DOI
  25. Katagiri K., Ueda Y., Tomiyama T., Yasuda K., Toda Y., Ikehara S., Nakayama K.I., and Kinashi T. 2011 Deficiency of Rap1-binding protein RAPL causes lymphoproliferative disorders through mislocalization of p27kip1. Immunity. 34: 24– 38. 10.1016/j.immuni.2010.12.010 21194982 · DOI
  26. Kerfoot S.M., and Kubes P. 2002 Overlapping roles of P-selectin and alpha 4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis. J. Immunol. 169: 1000– 1006. 10.4049/jimmunol.169.2.1000 12097407 · DOI
  27. Korn T., Fischer K.D., Girkontaite I., Köllner G., Toyka K., and Jung S. 2003 Vav1-deficient mice are resistant to MOG-induced experimental autoimmune encephalomyelitis due to impaired antigen priming. J. Neuroimmunol. 139: 17– 26. 10.1016/S0165-5728(03)00128-0 12799016 · DOI
  28. Krumbholz M., Theil D., Cepok S., Hemmer B., Kivisäkk P., Ransohoff R.M., Hofbauer M., Farina C., Derfuss T., Hartle C., 2006 Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 129: 200– 211. 10.1093/brain/awh680 16280350 · DOI
  29. Lambe T., Crawford G., Johnson A.L., Crockford T.L., Bouriez-Jones T., Smyth A.M., Pham T.H., Zhang Q., Freeman A.F., Cyster J.G., 2011 DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory. Eur. J. Immunol. 41: 3423– 3435. 10.1002/eji.201141759 21969276 PMC3517112 · DOI
  30. Li C., Jiao S., Wang G., Gao Y., Liu C., He X., Zhang C., Xiao J., Li W., Zhang G., 2015 a The immune adaptor ADAP regulates reciprocal TGF-β1-integrin crosstalk to protect from influenza virus infection. PLoS Pathog. 11: e1004824 10.1371/journal.ppat.1004824 25909459 PMC4409120 · DOI
  31. Li C., Li W., Xiao J., Jiao S., Teng F., Xue S., Zhang C., Sheng C., Leng Q., Rudd C.E., 2015 b ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy. EMBO Mol. Med. 7: 754– 769. 10.15252/emmm.201404578 25851535 PMC4459816 · DOI · Paper page
  32. Li W., Xiao J., Zhou X., Xu M., Hu C., Xu X., Lu Y., Liu C., Xue S., Nie L., 2015 c STK4 regulates TLR pathways and protects against chronic inflammation-related hepatocellular carcinoma. J. Clin. Invest. 125: 4239– 4254. 10.1172/JCI81203 26457732 PMC4639976 · DOI
  33. Lu M., Kinchen J.M., Rossman K.L., Grimsley C., Hall M., Sondek J., Hengartner M.O., Yajnik V., and Ravichandran K.S. 2005 A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. Curr. Biol. 15: 371– 377. 10.1016/j.cub.2005.01.050 15723800 · DOI · Paper page
  34. McFarland H.F., and Martin R. 2007 Multiple sclerosis: a complicated picture of autoimmunity. Nat. Immunol. 8: 913– 919. 10.1038/ni1507 17712344 · DOI · Paper page
  35. Medeiros R.B., Dickey D.M., Chung H., Quale A.C., Nagarajan L.R., Billadeau D.D., and Shimizu Y. 2005 Protein kinase D1 and the β1 integrin cytoplasmic domain control β1 integrin function via regulation of Rap1 activation. Immunity. 23: 213– 226. 10.1016/j.immuni.2005.07.006 16111639 · DOI
  36. Meisel M., Hermann-Kleiter N., Hinterleitner R., Gruber T., Wachowicz K., Pfeifhofer-Obermair C., Fresser F., Leitges M., Soldani C., Viola A., 2013 The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses. Immunity. 38: 41– 52. 10.1016/j.immuni.2012.09.021 23290522 PMC3556779 · DOI
  37. Meller N., Westbrook M.J., Shannon J.D., Guda C., and Schwartz M.A. 2008 Function of the N-terminus of zizimin1: autoinhibition and membrane targeting. Biochem. J. 409: 525– 533. 10.1042/BJ20071263 17935486 PMC2740492 · DOI
  38. Michel F., and Acuto O. 1996 Induction of T cell adhesion by antigen stimulation and modulation by the coreceptor CD4. Cell. Immunol. 173: 165– 175. 10.1006/cimm.1996.0264 8912873 · DOI
  39. Mou F., Praskova M., Xia F., Van Buren D., Hock H., Avruch J., and Zhou D. 2012 The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J. Exp. Med. 209: 741– 759. 10.1084/jem.20111692 22412158 PMC3328371 · DOI
  40. Paraboschi E.M., Rimoldi V., Soldà G., Tabaglio T., Dall’Osso C., Saba E., Vigliano M., Salviati A., Leone M., Benedetti M.D., 2014 Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis. Hum. Mol. Genet. 23: 6746– 6761. 10.1093/hmg/ddu392 25080502 · DOI
  41. Parekh D.B., Ziegler W., and Parker P.J. 2000 Multiple pathways control protein kinase C phosphorylation. EMBO J. 19: 496– 503. 10.1093/emboj/19.4.496 10675318 PMC305587 · DOI
  42. Parker P.J., and Murray-Rust J. 2004 PKC at a glance. J. Cell Sci. 117: 131– 132. 10.1242/jcs.00982 14676268 · DOI
  43. Randall K.L., Lambe T., Johnson A.L., Treanor B., Kucharska E., Domaschenz H., Whittle B., Tze L.E., Enders A., Crockford T.L., 2009 Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nat. Immunol. 10: 1283– 1291. 10.1038/ni.1820 19898472 PMC3437189 · DOI
  44. Randall K.L., Chan S.S., Ma C.S., Fung I., Mei Y., Yabas M., Tan A., Arkwright P.D., Al Suwairi W., Lugo Reyes S.O., 2011 DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. J. Exp. Med. 208: 2305– 2320. 10.1084/jem.20110345 22006977 PMC3201196 · DOI
  45. Ransohoff R.M., Kivisäkk P., and Kidd G. 2003 Three or more routes for leukocyte migration into the central nervous system. Nat. Rev. Immunol. 3: 569– 581. 10.1038/nri1130 12876559 · DOI · Paper page
  46. Shen Y., Li N., Wu S., Zhou Y., Shan Y., Zhang Q., Ding C., Yuan Q., Zhao F., Zeng R., and Zhu X. 2008 Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev. Cell. 14: 342– 353. 10.1016/j.devcel.2008.01.001 18331715 · DOI
  47. Sigal A., Bleijs D.A., Grabovsky V., van Vliet S.J., Dwir O., Figdor C.G., van Kooyk Y., and Alon R. 2000 The LFA-1 integrin supports rolling adhesions on ICAM-1 under physiological shear flow in a permissive cellular environment. J. Immunol. 165: 442– 452. 10.4049/jimmunol.165.1.442 10861083 · DOI
  48. Snelling S., Sinsheimer J.S., Carr A., and Loughlin J. 2007 Genetic association analysis of LRCH1 as an osteoarthritis susceptibility locus. Rheumatology (Oxford). 46: 250– 252. 10.1093/rheumatology/kel265 16891653 · DOI
  49. Sørensen T.L., Tani M., Jensen J., Pierce V., Lucchinetti C., Folcik V.A., Qin S., Rottman J., Sellebjerg F., Strieter R.M., 1999 Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J. Clin. Invest. 103: 807– 815. 10.1172/JCI5150 10079101 PMC408141 · DOI
  50. Steinman L. 2005 Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nat. Rev. Drug Discov. 4: 510– 518. 10.1038/nrd1752 15931259 · DOI
  51. Sun H., Liu J., Zheng Y., Pan Y., Zhang K., and Chen J. 2014 Distinct chemokine signaling regulates integrin ligand specificity to dictate tissue-specific lymphocyte homing. Dev. Cell. 30: 61– 70. 10.1016/j.devcel.2014.05.002 24954024 · DOI
  52. Tybulewicz V.L. 2005 Vav-family proteins in T-cell signalling. Curr. Opin. Immunol. 17: 267– 274. 10.1016/j.coi.2005.04.003 15886116 · DOI
  53. Vajkoczy P., Laschinger M., and Engelhardt B. 2001 Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J. Clin. Invest. 108: 557– 565. 10.1172/JCI12440 11518729 PMC209399 · DOI
  54. Wang H., and Rudd C.E. 2008 SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion. Trends Cell Biol. 18: 486– 493. 10.1016/j.tcb.2008.07.005 18760924 PMC3512129 · DOI
  55. Wang H., Moon E.Y., Azouz A., Wu X., Smith A., Schneider H., Hogg N., and Rudd C.E. 2003 SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates. Nat. Immunol. 4: 366– 374. 10.1038/ni913 12652296 · DOI
  56. Wang H., McCann F.E., Gordan J.D., Wu X., Raab M., Malik T.H., Davis D.M., and Rudd C.E. 2004 ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. J. Exp. Med. 200: 1063– 1074. 10.1084/jem.20040780 15477347 PMC2211848 · DOI
  57. Wang H., Liu H., Lu Y., Lovatt M., Wei B., and Rudd C.E. 2007 Functional defects of SKAP-55-deficient T cells identify a regulatory role for the adaptor in LFA-1 adhesion. Mol. Cell. Biol. 27: 6863– 6875. 10.1128/MCB.00556-07 17646386 PMC2099233 · DOI
  58. Wang H., Wei B., Bismuth G., and Rudd C.E. 2009 SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility. Proc. Natl. Acad. Sci. USA. 106: 12436– 12441. 10.1073/pnas.0900510106 19617540 PMC2710989 · DOI
  59. Wang H., Lim D., and Rudd C.E. 2010 Immunopathologies linked to integrin signalling. Semin. Immunopathol. 32: 173– 182. 10.1007/s00281-010-0202-3 20217414 · DOI
  60. Xu C., Gagnon E., Call M.E., Schnell J.R., Schwieters C.D., Carman C.V., Chou J.J., and Wucherpfennig K.W. 2008 Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. Cell. 135: 702– 713. 10.1016/j.cell.2008.09.044 19013279 PMC2597348 · DOI
  61. Yang H., Zhang T., Tao Y., Wang F., Tong L., and Ding J. 2013 Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair. Nucleic Acids Res. 41: 10573– 10583. 10.1093/nar/gkt788 24003026 PMC3905867 · DOI
  62. Zhang Y., and Wang H. 2012 Integrin signalling and function in immune cells. Immunology. 135: 268– 275. 10.1111/j.1365-2567.2011.03549.x 22211918 PMC3372743 · DOI
  63. Zhang Q., Davis J.C., Lamborn I.T., Freeman A.F., Jing H., Favreau A.J., Matthews H.F., Davis J., Turner M.L., Uzel G., 2009 Combined immunodeficiency associated with DOCK8 mutations. N. Engl. J. Med. 361: 2046– 2055. 10.1056/NEJMoa0905506 19776401 PMC2965730 · DOI
  64. Zhang Z., Zhang T., Wang S., Gong Z., Tang C., Chen J., and Ding J. 2014 Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5. eLife. 3: 3 10.7554/eLife.02687 PMC4102244 24957337 · DOI

Cited by

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Authors
Xu, X., Han, L., Zhao, G., Xue, S., Gao, Y., Xiao, J., Zhang, S., Chen, P., Wu, Z.-Y., Ding, J., Hu, R., Wei, B., & Wang, H.
Affiliations
  • Chinese Academy of Sciences (CN)
  • HuaShan Hospital, Fudan University, Shanghai 200031, China 4
  • University of Chinese Academy of Sciences (CN)
  • Second Affiliated Hospital of Zhejiang University (CN)
Corresponding author
Wang, Hongyan
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2016-12-27
Volume
214
Issue
1
Pages
209-226
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20160068
PMC
PMC5206493
OpenAlex
W2561977999
Cited by
53
References
2
Citations by year
2026: 9 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 8 · 2018: 3 · 2017: 3
FWCI
4.24
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Ministry of Science and Technology of China (2016YFD0500207, 2016YFC0902200, 2016YFD0500407)
  • Chinese Academy of Sciences (XDB19000000)
  • National Natural Science Foundation of China (31422018, 81630043, 81571617, 81571552, 31300723, 81671572, 81301027)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
DOCK8, Cdc42, T cell migration, experimental autoimmune encephalomyelitis, multiple sclerosis, protein kinase C alpha, guanine nucleotide exchange factor, chemokine signaling, serine phosphorylation, central nervous system infiltration
MeSH terms
Animals, Cell Movement, Encephalomyelitis, Autoimmune, Experimental, Mice, Inbred C57BL, Microfilament Proteins, Multiple Sclerosis, Phosphorylation, T-Lymphocytes, Guanine Nucleotide Exchange Factors, cdc42 GTP-Binding Protein, Mice, Protein Kinase C-alpha

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