CD22 Blockade Aggravates EAE and Its Role in Microglia Polarization

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2024 May 13

PMID 38739106

Authors

Weiwei Xiang

Kan Wang

Lu Han

Ze Wang

Zhiyang Zhou

Shuwei Bai

Jing Peng

Chong Xie

Yangtai Guan

Affiliations

Soon will be listed here.

Abstract

Aims: Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease. Microglia are reportedly involved in the pathogenesis of MS. However, the key molecules that control the inflammatory activity of microglia in MS have not been identified.

Methods: Experimental autoimmune encephalomyelitis (EAE) mice were randomized into CD22 blockade and control groups. The expression levels of microglial CD22 were measured by flow cytometry, qRT-PCR, and immunofluorescence. The effects of CD22 blockade were examined via in vitro and in vivo studies.

Results: We detected increased expression of microglial CD22 in EAE mice. In addition, an in vitro study revealed that lipopolysaccharide upregulated the expression of CD22 in microglia and that CD22 blockade modulated microglial polarization. Moreover, an in vivo study demonstrated that CD22 blockade aggravated EAE in mice and promoted microglial M1 polarization.

Conclusion: Collectively, our study indicates that CD22 may be protective against EAE and may play a critical role in the maintenance of immune homeostasis in EAE mice.

Citing Articles

CD22 blockade aggravates EAE and its role in microglia polarization.

Xiang W, Wang K, Han L, Wang Z, Zhou Z, Bai S CNS Neurosci Ther. 2024; 30(5):e14736.

PMID: 38739106 PMC: 11090149. DOI: 10.1111/cns.14736.

References

Glatigny S, Bettelli E . Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS). Cold Spring Harb Perspect Med. 2018; 8(11). PMC: 6211376. DOI: 10.1101/cshperspect.a028977. View

Wissfeld J, Nozaki I, Mathews M, Raschka T, Ebeling C, Hornung V . Deletion of Alzheimer's disease-associated CD33 results in an inflammatory human microglia phenotype. Glia. 2021; 69(6):1393-1412. DOI: 10.1002/glia.23968. View

Duan S, Paulson J . Siglecs as Immune Cell Checkpoints in Disease. Annu Rev Immunol. 2020; 38:365-395. DOI: 10.1146/annurev-immunol-102419-035900. View

Xie C, Li X, Zhou X, Li Z, Zhang Y, Zhao L . TGFβ1 transduction enhances immunomodulatory capacity of neural stem cells in experimental autoimmune encephalomyelitis. Brain Behav Immun. 2017; 69:283-295. DOI: 10.1016/j.bbi.2017.11.023. View

Thiesler H, Beimdiek J, Hildebrandt H . Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation. Cell Mol Life Sci. 2020; 78(4):1637-1653. PMC: 7904730. DOI: 10.1007/s00018-020-03601-z. View

LAWSON L, Perry V, Dri P, Gordon S . Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990; 39(1):151-70. DOI: 10.1016/0306-4522(90)90229-w. View

Clark E, Giltiay N . CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity. Front Immunol. 2018; 9:2235. PMC: 6173129. DOI: 10.3389/fimmu.2018.02235. View

Sucksdorff M, Tuisku J, Matilainen M, Vuorimaa A, Smith S, Keitila J . Natalizumab treatment reduces microglial activation in the white matter of the MS brain. Neurol Neuroimmunol Neuroinflamm. 2019; 6(4):e574. PMC: 6624093. DOI: 10.1212/NXI.0000000000000574. View

Symington F, Subbarao B, Mosier D, Sprent J . Lyb-8.2: A new B cell antigen defined and characterized with a monoclonal antibody. Immunogenetics. 1982; 16(5):381-91. DOI: 10.1007/BF00372098. View

10.

Petersen M, Ryu J, Akassoglou K . Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat Rev Neurosci. 2018; 19(5):283-301. PMC: 6743980. DOI: 10.1038/nrn.2018.13. View

11.

Xu F, Na L, Li Y, Chen L . Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci. 2020; 10(1):54. PMC: 7110906. DOI: 10.1186/s13578-020-00416-0. View

12.

Jie Z, Ko C, Wang H, Xie X, Li Y, Gu M . Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway. Sci Adv. 2021; 7(36):eabh0609. PMC: 8442891. DOI: 10.1126/sciadv.abh0609. View

13.

Correale J . The role of microglial activation in disease progression. Mult Scler. 2014; 20(10):1288-95. DOI: 10.1177/1352458514533230. View

14.

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

15.

Macauley M, Crocker P, Paulson J . Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014; 14(10):653-66. PMC: 4191907. DOI: 10.1038/nri3737. View

16.

Li Q, Cheng Z, Zhou L, Darmanis S, Neff N, Okamoto J . Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019; 101(2):207-223.e10. PMC: 6336504. DOI: 10.1016/j.neuron.2018.12.006. View

17.

Pluvinage J, Haney M, Smith B, Sun J, Iram T, Bonanno L . CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature. 2019; 568(7751):187-192. PMC: 6574119. DOI: 10.1038/s41586-019-1088-4. View

18.

Cougnoux A, Drummond R, Collar A, Iben J, Salman A, Westgarth H . Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention. Hum Mol Genet. 2018; 27(12):2076-2089. PMC: 5985727. DOI: 10.1093/hmg/ddy112. View

19.

Gao Z, Tsirka S . Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis. Neurol Res Int. 2011; 2011:383087. PMC: 3238412. DOI: 10.1155/2011/383087. View

20.

Airas L, Rissanen E, Rinne J . Imaging of microglial activation in MS using PET: Research use and potential future clinical application. Mult Scler. 2016; 23(4):496-504. DOI: 10.1177/1352458516674568. View