CD11b+GR1+ myeloid cells secrete NGF and promote trigeminal ganglion neurite growth: implications for corneal nerve regeneration.
OBJECTIVE
We characterized fluorescent bone marrow cells (YFP(+) BMCs) in the thy1-YFP mouse and determine if they promote trigeminal ganglion (TG) cell neurite growth.


METHODS
Excimer laser annular keratectomy was performed in thy1-YFP mice, and corneas were imaged. BMCs were harvested from femur and tibia, and the expression of surface markers on YFP(+) BMCs was analyzed by flow cytometry. The immunosuppressive action of BMCs (YFP(+) and YFP(-)) was evaluated in an allogenic mixed lymphocyte reaction (MLR). Neurotrophic action of BMCs (YFP(+) and YFP(-)) was determined in compartmental and transwell cultures of dissociated TG cells.


RESULTS
Following annular keratectomy, YFP(+) BMCs infiltrated the cornea. YFP(+) BMCs shared surface markers (CD11b+Gr1+Ly6C+Ly6G-F4/80(low)) with monocytic myeloid-derived suppressor cells (MDSCs), had similar morphology, and suppressed T-cell proliferation in allogenic MLR in a dose-dependent manner. YFP(+) BMCs, but not YFP(-) BMCs, significantly increased growth of TG neurites in vitro. When cultured in a transwell with TG neurites, YFP(+) BMCs expressed neurotrophins and secreted nerve growth factor (NGF) in conditioned medium. YFP(+) BMCs that infiltrated the cornea maintained their phenotype and actions (neuronal and immune).


CONCLUSIONS
YFP(+) BMCs in thy1-YFP mice have immunophenotypic features of MDSCs. They secrete NGF and promote neuroregeneration. Their immunosuppressive and neurotrophic actions are preserved after corneal infiltration. These findings increase our understanding of the beneficial roles played by leukocyte trafficking in the cornea and may lead to therapeutic strategies that use NGF-secreting myeloid cells to repair diseased or injured neurons.
Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
Joy
J
Sarkar
Shweta
S
Chaudhary
Sarmad H
SH
Jassim
Okan
O
Ozturk
Wallace
W
Chamon
Balaji
B
Ganesh
Sapna
S
Tibrewal
Sonal
S
Gandhi
Yong-Soo
YS
Byun
Joelle
J
Hallak
Dolores L
DL
Mahmud
Nadim
N
Mahmud
Damiano
D
Rondelli
Sandeep
S
Jain
D000818:Animals; D015153:Blotting, Western; D039481:CD11b Antigen / Q000276:immunology*; D002478:Cells, Cultured; D003315:Cornea / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D003316:Corneal Diseases / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051379:Mice; D018613:Microscopy, Confocal; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D014157:Transcription Factors / Q000276:immunology*; D012668:Trigeminal Ganglion / Q000254:growth & development*
D039481:CD11b Antigen; D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors; D020932:Nerve Growth Factor
cornea; inflammation; myeloid cell; nerve regeneration