Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea.
Immune-mediated inner ear disorder has been well established as a clinical entity; however, the innate immune system of the inner ear is a poorly understood area of research with high clinical and immunological importance. Although the presence of resident tissue macrophages in the inner ear has been suggested, there has been some controversy. In this study, we analyzed the origin of cochlear resident macrophages and the contribution of hematopoietic bone marrow (BM) to the recruitment of macrophages in the cochlea. To visualize the localization of BM-derived cells, BM chimeric mice were made by transplantation of hematopoietic stem cells, which were genetically labeled with enhanced green fluorescent protein, into lethally irradiated C57BL/6 mice. The distribution and characteristics of BM-derived cells in the mouse cochlea were studied immunohistochemically. We successfully identified the constitutive presence of tissue resident macrophages in the spiral ligament and spiral ganglion that are derived from BM in larger numbers than previously reported. Moreover, cochlear resident macrophages gradually turn over for several months during steady-state replacement by BM-derived cells, and the number of cochlear macrophages immediately increased in response to local surgical stress. The present findings demonstrate the hematopoietic origin of cochlear resident and infiltrating macrophages. Our study provides a novel anatomical and immunological basis for the inner ear and indicates that the cochlear resident macrophages would be a therapeutic target in inner ear disorders.
Okano
Takayuki
T
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nakagawa
Takayuki
T
Kita
Tomoko
T
Kada
Shinpei
S
Yoshimoto
Momoko
M
Nakahata
Tatsutoshi
T
Ito
Juichi
J
D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003051:Cochlea / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins