Cellular Expression of LRRFIP1 and Its Potential Role in CNS Immune Responses.

Abstract

Cellular Expression of LRRFIP1 and Its Potential Role in CNS Immune Response Bai J-Z, Fowke T, Ranchhod S, Gunn K and Dean J. The Centre for Brain Research and Department of Physiology, University of Auckland, Auckland, New Zealand In peripheral immune cells, LRRFIP1 [leucine-rich repeat (in FLII) interacting protein 1] is an intracellular nucleic acid sensor that detects microbial RNA and DNA, resulting in release of proinflammatory cytokines. LRRFIP1 is also recruited as part of the toll-like receptor (TLR) signaling pathway that plays a key role in innatre immunity. It is well established that TLR signalling is also important for controlling innate immunity and inflammation in the CNS. However, a role for LRRFIP1 in the CNS immune response remains unknown. Thus, we examined the cellular expression of LRRFIP1 in the developing brain, and its regualtion following CNS inflammation. Brains from Sprague Dawley (SD) rats were collected at postnatal days 1 (P1), P4, and P14, and fixed in 4% PFA. Colocalisation of LRRFIP1 with neurons/neuronal processes (NeuN, Map2), oligodendrocytes (olig2), and microglia (Iba1) was examined using immunohistochemistry and confocal microscopy. In a second set of experiments, P1 rats were exposed to the potent TLR4 agonist lipopolysaccharide (LPS), and the brains collected at P2, P7, and P14 for real-time PCR (qPCR) analysis of LRRFIP1 mRNA expression. By immunohistochemistry, LRRFIP1 showed colocalisation with (1) developing microglial cells, (2) mature oligodendrocytres, (3) and the apical dendrite of a subpopulation of mature cortical layer 5 pyramidal neurons. Following exposure to LPS, there was also a significant increase in the expression of LRRFIP1 mRNA in the brain (~2-fold). These preliminary results suggest that LRRFIP1 is differentially expressed in microglia, oligodendrocytes and pyramidal neurons of the rat brain, and also forms part of CNS inflammatory signalling response. Studies examining the specific cellular role of LRRFIP1 in the development brain and in response to inflammation are ongoing.