Brain specific IL-2 delivery as novel strategy
to prevent pathological neuroinflammation
(Prof. Pasciuto)
1. Neuroinflammation
Inflammation: host defense response to injury, tissue ischemia, stress,
autoimmune response or infectious agents
o Swelling, redness, heat, pain in various tissues but
Neuroinflammation: host defense response to injury, tissue ischemia,
stress, autoimmune response or infectious agents etc
o Pain, Neurodegeneration, Cognitive impairment, Motor impairment
etc.
Important cells
o Glial cells activation
o Cytokine release
o Endothelial cells activation
o Rupture of the BBB
o Proliferation and recruitment of immune cells
o Neuronal damage
NO CURE at the moment
1.1. Challenges of therapeutic interventions in
neuroinflammation
Central role of neuro inflammation in brain disorders has only recently
been established.
In chronic inflammation the inflammation starts before the symptoms >>>
delayed intervention
In acute inflammation, in most cases prevention is not possible
Mechanisms?
1.2. Targeting T-cells to prevent neuroinflammation
Genetic, clinical, and experimental studies shows that both the innate and
the adaptive immune system influence neuroinflammation and
neurodegeneration
Neuroinflammation, immune cells activation and recruitment
GWAS identified specific genetic variations (HLA-DR; IL17A; IL10;CD25,
KIR) association to brain disorders
Biomarker of disease (CSF and blood)
Clinical trials ongoing to target Adaptive immune system in AD, psychosis
and Autism (e.g. IL2, Tregs
Effector T cells (CD4 and CD8 T cells)
o Recruit other immune cells
o Cytotoxic
o Pro-inflammatory
Regulatory T cells (CD4 T cells)
o Immune regulation
1
, o Tissue homeostasis and repair
o Anti-inflammatory
2
to prevent pathological neuroinflammation
(Prof. Pasciuto)
1. Neuroinflammation
Inflammation: host defense response to injury, tissue ischemia, stress,
autoimmune response or infectious agents
o Swelling, redness, heat, pain in various tissues but
Neuroinflammation: host defense response to injury, tissue ischemia,
stress, autoimmune response or infectious agents etc
o Pain, Neurodegeneration, Cognitive impairment, Motor impairment
etc.
Important cells
o Glial cells activation
o Cytokine release
o Endothelial cells activation
o Rupture of the BBB
o Proliferation and recruitment of immune cells
o Neuronal damage
NO CURE at the moment
1.1. Challenges of therapeutic interventions in
neuroinflammation
Central role of neuro inflammation in brain disorders has only recently
been established.
In chronic inflammation the inflammation starts before the symptoms >>>
delayed intervention
In acute inflammation, in most cases prevention is not possible
Mechanisms?
1.2. Targeting T-cells to prevent neuroinflammation
Genetic, clinical, and experimental studies shows that both the innate and
the adaptive immune system influence neuroinflammation and
neurodegeneration
Neuroinflammation, immune cells activation and recruitment
GWAS identified specific genetic variations (HLA-DR; IL17A; IL10;CD25,
KIR) association to brain disorders
Biomarker of disease (CSF and blood)
Clinical trials ongoing to target Adaptive immune system in AD, psychosis
and Autism (e.g. IL2, Tregs
Effector T cells (CD4 and CD8 T cells)
o Recruit other immune cells
o Cytotoxic
o Pro-inflammatory
Regulatory T cells (CD4 T cells)
o Immune regulation
1
, o Tissue homeostasis and repair
o Anti-inflammatory
2
