Origin, dynamics and transcriptional profile of dorsal root ganglion and sciatic nerve macrophages in homeostasis and during neuropathic pain

• Grant number: 20/05446-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2020
• End date: September 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Conceição Elidianne Aníbal Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 23/02849-5 - Origin and dynamics of sensory neuron-associated macrophages (sNAMs), BE.EP.DD

Abstract

Macrophages are cellular components of the immune system that reside in the most diverse tissues, being described as cells that play a fundamental role in several processes of immune responses such as maintaining homeostasis and modulating inflammatory processes. The concept that all macrophages residing in tissues are derived from bone marrow precursors and intermediate circulating monocytes has changed dramatically in recent years. Recent observations indicate that macrophages residing in some tissues come from embryonic parents, persist in adulthood, having the power of self-maintenance and extensive local proliferation. However, in many tissues the origin of these macrophages is not yet known, making studies necessary to unveil their origin and dynamics. The CX3CR1+ macrophages residing in the Dorsal Root Ganglia (DRGs) and the sciatic nerve are at the interface of the peripheral nervous system and are closely related to the neuro-immunological responses in these locations, however their origin remains unknown, so their role in the pathways of triggering and maintenance of pain. Given this information, we propose in the present project, to investigate the origin of the resident macrophages of the GRDs and the sciatic Nerve, to characterize phenotypically and morphologically this highly specific cell population, as well as to understand the dynamics of these macrophages in the tissues. In parallel, we will analyze the transcriptional profile of the resident macrophages of the GRDs and sciatic nerve, in conditions of homeostasis and in animals subjected to peripheral nerve damage (neuropathic pain model), comparing with different types of resident macrophages (eg. Microglia), information that which may provide important data on the network of interaction and gene regulation of these cells in a physiological and neuroimmune disorder condition, in order to understand the pathways that contribute to the triggering and maintenance of pain.The elucidation of the origin of these macrophages would add an unprecedented concept in the field of immunology research, serving as a basis for the development of several researches. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANIBAL SILVA, CONCEICAO ELIDIANNE; GUIMARAES, RAFAELA MANO; CUNHA, THIAGO MATTAR. Sensory neuron-associated macrophages as novel modulators of neuropathic pain. PAIN REPORTS, v. 6, n. 1, 2021. (20/05446-0, 13/08216-2, 19/13829-0, 17/50419-9)