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Agrin is involved in lymphocytes activation that is mediated by -dystroglycan

Jinping Zhang^*, Ying Wang^*, Yiwei Chu^*, Liping Su^*, Yanping Gong^*, Ruihua Zhang^* and Sidong Xiong^*,,1

^* Department of Immunology and Key Laboratory of Molecular Medicine of the Ministry of Education, Shanghai Medical College of Fudan University, Shanghai, China; and
Immunology Division of E-Institutes of Shanghai Universities, Shanghai, China

¹Correspondence: Department of Immunology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. E-mail: sdxiongfd{at}126.com

It is well established that agrin, an extracellular matrix protein, plays a crucial role in the formation of neuromuscular junctions. Recent evidence indicates that agrin also contributes to immunological synapse formation. However, little is known about how agrin induces the activation of lymphocytes and whose receptors mediate its regulatory effects on these cells. In the present study, agrin was detected in lymphocytes. Up-regulation of agrin expression was involved in lymphocyte activation whereas down-regulation of its expression led to inhibition of both antigen-specific and nonspecific lymphocyte activation, indicating an intrinsic role for agrin in the activation of lymphocytes. Unexpectedly, unlike that found in muscle cells where there is coexpression of muscle-specific kinase (MuSK) and -dystroglycan receptors for agrin, only -dystroglycan could be detected in lymphocytes. Confocal examination showed that -dystroglycan colocalized with agrin in forming the immunological synapse. Down-regulation of -dystroglycan expression inhibited lymphocyte activation even in the presence of agrin. However, agrin involved in down-regulation of -dystroglycan receptors did not increase the inhibitory effect on lymphocytes activation. The anti--dystroglycan antibody also induced lymphocytes activation. Taken together, these findings strongly indicate that agrin and -dystroglycan mediate lymphocyte activation. Furthermore, agrin-involved lymphocyte activation is mediated by -dystroglycan.—Zhang, J., Wang, Y., Chu, Y., Su, L., Gong, Y., Zhang, R., Xiong, S. Agrin is involved in lymphocytes activation that is mediated by -dystroglycan.

Key Words: agrin • -dystroglycan • Immunological synapse • lymphocyte activation

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