Deficiency of IκB Kinase in Myeloid Cells Reduces Severity of Experimental Autoimmune Encephalomyelitis.

Deficiency of IκB Kinase in Myeloid Cells Reduces Severity of Experimental Autoimmune Encephalomyelitis.
Am J Pathol. 2016 Mar 8;
Authors: Hao W, Decker Y, Schnöder L, Schottek A, Li D, Menger MD, Fassbender K, Liu Y
Abstract
In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), peripherally developed myelin-reactive T lymphocytes stimulate myeloid cells (ie, microglia and infiltrated macrophages) to trigger an inflammatory reaction in the central nervous system, resulting in demyelination and neurodegeneration. IκB kinase (IKKβ) is a kinase that modulates transcription of inflammatory genes. To investigate the pathogenic role of IKKβ in MS, we developed strains in which IKKβ was conditionally ablated in myeloid cells and established active or passive EAE in these animals. Deficiency of IKKβ in myeloid cells ameliorated EAE symptoms and suppressed neuroinflammation, as shown by decreased infiltration of T lymphocytes and macrophages and reduced inflammatory gene transcription in the spinal cord at the peak or end stage of EAE. Myeloid deficiency of IKKβ also reduced the transcription of rorc or il17 genes in T lymphocytes isolated from lymph nodes, spleen, and spinal cord of EAE mice. Moreover, cultured splenocytes isolated from myeloid IKKβ-deficient EAE mice released less IL-17, interferon-γ, and granulocyte-macrophage colony-stimulating factor after treatment with myelin peptide...

Source: The American Journal of Pathology - March 8, 2016 Category: Pathology Authors: Hao W, Decker Y, Schnöder L, Schottek A, Li D, Menger MD, Fassbender K, Liu Y Tags: Am J Pathol Source Type: research