Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3-expressing microglia.

What mechanism that determines microglia accomplishing destructive or constructive role in CNS remains nebulous. We report here that intracranial priming and rechallenging with Toxoplasma gondii in mice elicit neurotoxic CCR9+ Irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis and produce a high level of TNF-alpha; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive CXCR3+ Irg1- microglia, which are sensitive to apoptosis and produce a high level of IL-10 and TGF-beta. Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- microglia in vivo. Moreover, by using a series of different neurotropic pathogens, including intracellular parasites, chronic virus, bacteria, toxic substances, and CNS injury to intracranially prime and subsequent rechallenge mice, the bi-directional elicitation of microglia has been confirmed as neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- cells in these mouse models. These data suggest that there exist two different types of microglia, providing with a novel insight into microglial involvement in neurodegenerative and neuroinflammatory pathogenesis such as Alzheimer's disease and AIDS dementia.

V alpha 24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement.

We have demonstrated that Valpha24(+)Vbeta11(+) invariant (Valpha24(+)i) NKT cells from patients with allergic asthma express CCR9 at high frequency. CCR9 ligand CCL25 induces chemotaxis of asthmatic Valpha24(+)i NKT cells but not the normal cells. A large number of CCR9-positive Valpha24(+)i NKT cells are found in asthmatic bronchi mucosa, where high levels of Th2 cytokines are detected. Asthmatic Valpha24(+)i NKT cells, themselves Th1 biased, induce CD3(+) T cells into an expression of Th2 cytokines (IL-4 and IL-13) in cell-cell contact manner in vitro. CD226 are overexpressed on asthmatic Valpha24(+)i NKT cells. CCL25/CCR9 ligation causes directly phosphorylation of CD226, indicating that CCL25/CCR9 signals can cross-talk with CD226 signals to activate Valpha24(+)i NKT cells. Prestimulation with immobilized CD226 mAb does not change ability of asthmatic Valpha24(+)i NKT cells to induce Th2-cytokine production, whereas soluble CD226 mAb or short hairpin RNA of CD226 inhibits Valpha24(+)i NKT cells to induce Th2-cytokine production by CD3(+) T cells, indicating that CD226 engagement is necessary for Valpha24(+)i NKT cells to induce Th2 bias of CD3(+) T cells. Our results are providing with direct evidence that aberration of CCR9 expression on asthmatic Valpha24(+)i NKT cells. CCL25 is first time shown promoting the recruitment of CCR9-expressing Valpha24(+)i NKT cells into the lung to promote other T cells to produce Th2 cytokines to establish and develop allergic asthma. Our findings provide evidence that abnormal asthmatic Valpha24(+)i NKT cells induce systemically and locally a Th2 bias in T cells that is at least partially critical for the pathogenesis of allergic asthma.

The changes of functions of chemokine receptor 9 on T cell lymphocytic leukemia patients / 中国免疫学杂志

Objective:To observe the influences of functions of chemokine receptor 9(CCR9) on leukemia patients,we analyzed 38 typical T cell lymphocytic leukemia cases.Methods:The functions of T ALL and T CLL CD4+T cells towards TECK/CCL25 were determined by chemotaxis assay and adhesion assay.Results:Almost in all of the T ALL patients,TECK/CCL25(a ligand for CCR9)could induce a high chemotactic migration of T ALL CD4+ cells as well as a high adhesion.Conclusion:It indicates that CCR9 and its ligands may promote survival or proliferation of T ALL cells. [

CCR7~+CD8~+CD45RO~+ T Cells induced Differentiation of CD4~+T Cells to Th2 Cells in Active Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To determine the functions of CCR7+CD8+CD45RO+ T cells on CD4+T cells in systemic lupus erythematosu(SLE).Methods The expres sion of cytokines in CD4+T cells was measured by flow cytometry,real-time qua ntitative reverse transcription polymerase chain reaction and Northern blotting.A chemotaxis assay was used to detect their functions.Results In the case of active SLE,CCR7+CD8+CD45RO+T cells could induce CD4+T cells to express high le vels of Th2-cytokine (IL-4),and low levels of Tr1-cytokines (IL-10 and TGF-?),than those in normal controls and inactive SLE (P