Neuroimmunology of the Interleukins 13 and 4

Abstract

The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 pro-inflammatory cytokines. Their presence and role in the brain is only beginning to be investigated and the data collected so far shows that these molecules can be produced by microglial cells and possibly by neurons. Attention has so far been given to the possible role of these molecules in neurodegeneration. Both neuroprotective or neurotoxic effects have been proposed based on evidence that interleukin 13 and 4 can reduce inflammation by promoting the M2 microglia phenotype and contributing to the death of microglia M1 phenotype, or by potentiating the effects of oxidative stress on neurons during neuro-inflammation. Remarkably, the heterodimeric subunit IL-13Rα1 of their common receptor was recently demonstrated in dopaminergic neurons of the ventral tegmental area and the substantia nigra pars compacta, suggesting the possibility that both cytokines may affect the activity of these neurons regulating reward, mood, and motor coordination. In mice and man, the gene encoding for IL-13Rα1 is expressed on the X chromosome within the PARK12 region of susceptibility to Parkinson’s disease (PD). This, together with finding that IL-13Rα1 contributes to loss of dopaminergic neurons during inflammation, indicates the possibility that these cytokines may contribute to the etiology or the progression of PD.

Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

“…Furthermore, the positive correlations of Th2 cytokines (IL‐13 and CCL11/eotaxin) with CSF cell counts and protein amounts and reduction of IL‐13 levels during longitudinal follow‐up after immunotherapy in NF155 + CIDP suggested the involvement of Th2 cells in spinal root inflammation, in addition to the induction of IgG4 autoantibodies. In Th2 inflammation, IL‐13 is a major effector cytokine, while CCL11/eotaxin exhibits potent chemotactic activity …”

Type 2/Th2‐driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model

“…These different induction strategies might result in differential cytokine profiles (T helper 1 [Th1], Th2, Th1/Th2‐mixed, or T helper 17 [Th17]) that could differently impact OSN survival or renewal. For example, a study by Mori et al suggests that IL‐4 and IL‐13 cytokines could contribute to pathological mechanisms leading to the loss of dopaminergic neurons in Parkinson's disease. Interestingly, IL‐13Rα 1 and IL‐4Rα mRNAs are detected in mature OSNs as well as in HBCs and GBCs, which are involved in OSN renewal.…”

Time Course of Blood and Brain Cytokine/Chemokine Levels Following Adolescent Alcohol Exposure and Withdrawal in Rats

“…We sought to determine how widespread microglial activation might be in brain following alcohol exposure. The specific brain regions were selected based on our previous studies demonstrating that these brain areas are important in neuroimmune functions as well as sensitive to the effects of alcohol (Alboni et al, ; Amodeo et al, ; Ehlers et al, ; Ehlers et al, ; Ehlers et al, ; Hwang et al, ; Mori et al, ; Mori et al, ; Morrison et al, ; Sugama et al, ; Sugama et al, ).…”