Multiple sclerosis (MS) is a progressive, neurodegenerative disease of the central nervous system (CNS) perpetuated by autoreactive immune cells that destroy myelin. Despite many advances in the treatment of MS, there are currently no approved therapies aimed at protecting or restoring the CNS to promote patient recovery. Many current treatments for MS impair the immune response; however, recent evidence suggests that immune molecules called cytokines may influence the development of new myelin in the context of MS. We aim to further understand the interplay between the immune and central nervous systems during MS in order to uncover novel therapeutic options for MS patients.
More specifically, we are interested in how cytokines mediate neuroimmune crosstalk to facilitate CNS repair. Cytokines and their receptors are expressed in and around MS lesions by immune cells and glia, critical CNS cells that maintain homeostasis, support blood-brain barrier function, and provide neuronal support. However, we know relatively little about how these functions change in response to inflammation. Further, we have shown that glia, including astrocytes, oligodendrocytes, and their progenitors, exhibit heterogeneity between regions of the CNS, as well as differential responses to cytokines. Thus, a second focus of the Williams Lab is to determine how regionally distinct populations of glia communicate with immune cells to mediate autoimmune processes during MS pathogenesis and recovery.
Daniels BP, Jujjavarapu H, Durrant DM, Williams JL, Green RR, White JP, Lazear HM, Gale M Jr, Diamond MS, Klein RS. (2017) Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection. J Clin Invest 127(3):843-856. PMID: 28134626; PMCID: PMC5330728
Williams JL, Holman DW, Klein RS. (2014) Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers. Front Cell Neurosci 8:154. PMID: 24920943; PMCID: PMC4036130
Williams JL, Patel JR, Daniels BP, Klein RS. (2014) Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the adult central nervous system. J Exp Med 211(5):791-9. PMID: 24733828; PMCID: PMC4010893
Durrant DM, Williams JL, Daniels BP, Klein RS. (2014) Chemokines Referee Inflammation within the Central Nervous System during Infection and Disease. Adv Med 2014:806741. PMID: 26556427; PMCID: PMC4590974
Cox GM, Kithcart AP, Pitt D, Guan Z, Alexander J, Williams JL, Shawler T, Dagia NM, Popovich PG, Satoskar AR, Whitacre CC. (2013) Macrophage migration inhibitory factor potentiates autoimmune-mediated neuroinflammation.J Immunol 191(3):1043-54. PMID: 23797673
Williams JL, Gatson NN, Smith KM, Almad A, McTigue DM, Whitacre CC. (2013) Serum exosomes in pregnancy-associated immune modulation and neuroprotection during CNS autoimmunity. Clin Immunol 149(2):236-43. PMID: 23706172; PMCID: PMC3778091
Patel JR, Williams JL, Muccigrosso MM, Liu L, Sun T, Rubin JB, Klein RS. (2012) Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS. Acta Neuropathol 124(6):847-60. PMID: 22933014; PMCID: PMC3508279
Smith KM, Guerau-de-Arellano M, Costinean S, Williams JL, Bottoni A, Mavrikis Cox G, Satoskar AR, Croce CM, Racke MK, Lovett-Racke AE, Whitacre CC. (2012) miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. J Immunol 189(4):1567-76. PMID: 22772450; PMCID: PMC3411895
Williams JL, Richert BT, Marchant-Forde JN, Eicher SD. (2012) Behavioral changes in neonatal swine after an 8-hour rest during prolonged transportation. J Anim Sci 90(9):3213-9. PMID: 22966080
Williams JL, Kithcart AP, Smith KM, Shawler T, Cox GM, Whitacre CC. (2011) Memory cells specific for myelin oligodendrocyte glycoprotein (MOG) govern the transfer of experimental autoimmune encephalomyelitis. J Neuroimmunol 234(1-2):84-92. PMID: 21463904; PMCID: PMC3690522
Gatson NN, Williams JL, Powell ND, McClain MA, Hennon TR, Robbins PD, Whitacre CC. (2011) Induction of pregnancy during established EAE halts progression of CNS autoimmune injury via pregnancy-specific serum factors. J Neuroimmunol 230(1-2):105-13. PMID: 20950868; PMCID: PMC3021646
Williams JL, Minton JE, Patterson JA, Marchant Forde J, Eicher SD. (2008) Lairage during transport of eighteen-kilogram pigs has an impact on innate immunity and commensal bacteria diversity in the intestines. J Anim Sci 86(5):1232-44. PMID: 18245499