期刊
JOURNAL OF AUTOIMMUNITY
卷 133, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2022.102945
关键词
Immune-mediated neuropathies; Guillain-Barre syndrome; Experimental autoimmune neuritis; Monocyte conversion; Notch signaling; NR4A1
类别
资金
- National Natural Science Foundation of China [82171339]
- Key Research and Development Project of Shaanxi Province [2022ZDLSF02-04, 2022SF-167]
The conversion of monocytes modulated by Notch signaling plays a crucial role in the mouse model of experimental autoimmune neuritis.
Monocytes in peripheral blood and sciatic nerves play vital roles in immune-mediated neuropathies such as Guillain-Barre syndrome (GBS). Different subpopulations of monocytes, including classical and non-classical, exhibit distinct functions as well as phenotypic conversion potentials. However, the mechanisms underlying their development during immune-mediated neuropathy remain unclear. Notch signaling participates in monocyte differentiation and function. In this study, we used a myeloid-specific Notch signaling activation transgenic mouse (NICcA) and investigated the role of Notch signaling in monocytes during experimental autoimmune neuritis (EAN) in a mouse model of GBS. Clinical score assessment and histopathological examination revealed that sciatic nerve injury was attenuated in NICcA EAN mice compared to that in control mice. Flow cytometry and immunofluorescence staining suggested that increasing Ly6C(lo) monocytes in the peripheral blood and nerve tissue might contribute to the alleviation of neuritis in NICcA mice. Meanwhile, an in vitro study suggested that bone marrow-derived monocytes from NICcA mice are more inclined toward Ly6C(lo) cells than Ly6C(hi) cells. Differential expression of monocyte development-associated genes was detected in NICcA and wildtype mice using RNA sequencing. The expression of Nr4a1 is upregulated remarkably when Notch signaling is activated. Treatment with Nr4a1 antagonist on NICcA mice-derived monocytes compromise their Ly6C(lo) tendency. Consistently, a relationship between monocyte conversion and disease severity was observed in blood samples from patients with GBS. In conclusion, our current study showed that monocyte conversion modulated by Notch signaling plays an essential role in the EAN mouse model.
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