TY - JOUR
T1 - Tetraspanin CD53 modulates lymphocyte trafficking but not systemic autoimmunity in Lyn-deficient mice
AU - Yeung, Louisa
AU - Gottschalk, Timothy A.
AU - Hall, Pam
AU - Tsantikos, Evelyn
AU - Gallagher, Rebecca H.
AU - Kitching, A. Richard
AU - Hibbs, Margaret L.
AU - Wright, Mark D.
AU - Hickey, Michael J.
N1 - Funding Information:
The authors acknowledge the kind assistance of technicians at the Monash Animal Research Platform, Clayton and AMREP Animal Services, Prahran, the staff at AMREP FlowCore facility and Monash Micro Imaging, Monash University, for the provision of instrumentation, training and technical support. This work was supported by funding from the National Health and Medical Research Council (NHMRC), Australia (Project Grant IDs 1033198 to MDW & 1124459 to MJH & ARK; Senior Research Fellowship ID 1042775 to MJH) and the Central Clinical School, Monash University (MLH, MDW).
Publisher Copyright:
© 2021 Australian and New Zealand Society for Immunology Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - The leukocyte-restricted tetraspanin CD53 has been shown to promote lymphocyte homing to lymph nodes (LNs) and myeloid cell recruitment to acutely inflamed peripheral organs, and accelerate the onset of immune-mediated disease. However, its contribution in the setting of chronic systemic autoimmunity has not been investigated. We made use of the Lyn−/− autoimmune model, generating Cd53−/−Lyn−/− mice, and compared trafficking of immune cells into secondary lymphoid organs and systemic autoimmune disease development with mice lacking either gene alone. Consistent with previous observations, absence of CD53 led to reduced LN cellularity via reductions in both B and T cells, a phenotype also observed in Cd53−/−Lyn−/− mice. In some settings, Cd53−/−Lyn−/− lymphocytes showed greater loss of surface L-selectin and CD69 upregulation above that imparted by Lyn deficiency alone, indicating that absence of these two proteins can mediate additive effects in the immune system. Conversely, prototypical effects of Lyn deficiency including splenomegaly, plasma cell expansion, elevated serum immunoglobulin M and anti-nuclear antibodies were unaffected by CD53 deficiency. Furthermore, while Lyn−/− mice developed glomerular injury and showed elevated glomerular neutrophil retention above than that in wild-type mice, absence of CD53 in Lyn−/− mice did not alter these responses. Together, these findings demonstrate that while tetraspanin CD53 promotes lymphocyte trafficking into LNs independent of Lyn, it does not make an important contribution to development of autoimmunity, plasma cell dysfunction or glomerular injury in the Lyn−/− model of systemic autoimmunity.
AB - The leukocyte-restricted tetraspanin CD53 has been shown to promote lymphocyte homing to lymph nodes (LNs) and myeloid cell recruitment to acutely inflamed peripheral organs, and accelerate the onset of immune-mediated disease. However, its contribution in the setting of chronic systemic autoimmunity has not been investigated. We made use of the Lyn−/− autoimmune model, generating Cd53−/−Lyn−/− mice, and compared trafficking of immune cells into secondary lymphoid organs and systemic autoimmune disease development with mice lacking either gene alone. Consistent with previous observations, absence of CD53 led to reduced LN cellularity via reductions in both B and T cells, a phenotype also observed in Cd53−/−Lyn−/− mice. In some settings, Cd53−/−Lyn−/− lymphocytes showed greater loss of surface L-selectin and CD69 upregulation above that imparted by Lyn deficiency alone, indicating that absence of these two proteins can mediate additive effects in the immune system. Conversely, prototypical effects of Lyn deficiency including splenomegaly, plasma cell expansion, elevated serum immunoglobulin M and anti-nuclear antibodies were unaffected by CD53 deficiency. Furthermore, while Lyn−/− mice developed glomerular injury and showed elevated glomerular neutrophil retention above than that in wild-type mice, absence of CD53 in Lyn−/− mice did not alter these responses. Together, these findings demonstrate that while tetraspanin CD53 promotes lymphocyte trafficking into LNs independent of Lyn, it does not make an important contribution to development of autoimmunity, plasma cell dysfunction or glomerular injury in the Lyn−/− model of systemic autoimmunity.
KW - cell migration
KW - inflammation
KW - lupus nephritis
KW - lymphocyte activation
KW - mechanisms of disease
KW - systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85116836212&partnerID=8YFLogxK
U2 - 10.1111/imcb.12501
DO - 10.1111/imcb.12501
M3 - Article
C2 - 34514627
AN - SCOPUS:85116836212
VL - 99
SP - 1053
EP - 1066
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
SN - 0818-9641
IS - 10
ER -