Differential Activation States of Direct Pathway Striatal Output Neurons during l-DOPA-Induced Dyskinesia Development.

l-DOPA-induced dyskinesia (LID) is a debilitating motor side effect arising from chronic dopamine (DA) replacement therapy with l-DOPA for the treatment of Parkinson's disease. LID is associated with supersensitivity of striatal dopaminergic signaling and fluctuations in synaptic DA following each l-DOPA dose, shrinking the therapeutic window. The heterogeneous composition of the striatum, including subpopulations of medium spiny output neurons (MSNs), interneurons, and supporting cells, complicates the identification of cell(s) underlying LID.

Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence.

Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier. T cells, but not innate lymphoid cells, have an indispensable role in sustaining the IL-22 signalling that is required for the protection of colonic crypts against invasion during infection by the enteropathogen Citrobacter rodentium (Cr). However, the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22, and how T cell-derived IL-22 sustains activation in IECs, remain undefined.

IL-2-induced Stat3 Signaling is Critical for Effector Treg Cell Programming.

Maintenance of immune homeostasis to the intestinal mictrobiota is dependent on a population of effector regulatory T (eTreg) cells that develop from microbiota-reactive induced (i)Treg cells. A cardinal feature of eTreg cells is their production of IL-10, which plays a non-redundant role in immune tolerance of commensal microbes. Here, we identify an unexpected role for IL-2-induced Stat3 signaling to program iTreg cells for eTreg cell differentiation and transcriptional competency.

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease.

Dopaminergic cell loss due to the accumulation of α-syn is a core feature of the pathogenesis of Parkinson disease. Neuroinflammation specifically induced by α-synuclein has been shown to exacerbate neurodegeneration, yet the role of central nervous system (CNS) resident macrophages in this process remains unclear. We found that a specific subset of CNS resident macrophages, border-associated macrophages (BAMs), play an essential role in mediating α-synuclein related neuroinflammation due to their unique role as the antigen presenting cells necessary to initiate a CD4 T cell response whereas the loss of MHCII antigen presentation on microglia had no effect on neuroinflammation.

Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4 T cell fate.

Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1CXCR5Bcl6CD4 T cells will differentiate into PD-1CXCR5Bcl6 GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1CXCR5CD4 T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas TigitPD-1CXCR5CD4 T cells upregulate IL-7Rα to become CXCR5CD4 T memory cells with or without CCR7.