TY - JOUR
T1 - Cxcl17 −/− mice develop exacerbated disease in a T cell-dependent autoimmune model
AU - Hernández-Ruiz, Marcela
AU - Othy, Shivashankar
AU - Herrera, Carolina
AU - Nguyen, Hong Tam
AU - Arrevillaga-Boni, Gerardo
AU - Catalan-Dibene, Jovani
AU - Cahalan, Michael D.
AU - Zlotnik, Albert
N1 - Publisher Copyright:
© 2019 Society for Leukocyte Biology
PY - 2019/5
Y1 - 2019/5
N2 - CXCL17 is a homeostatic chemokine in the mucosa known to chemoattract dendritic cells and macrophages but can also be expressed elsewhere under inflammatory conditions. Cxcl17 −/− mice have lower numbers of macrophages or dendritic cells in mucosal tissues. CXCL17 is also able to chemoattract suppressor myeloid cells that can recruit regulatory T cells. To explore a possible role of Cxcl17 in T cells, we studied T cell populations from Cxcl17 −/− or wild-type (WT) littermate mice. Cxcl17 −/− mice have higher numbers of CD4 + and CD8 + T cells in spleen and lymph nodes (LNs). Upon activation, they produce higher levels of several proinflammatory cytokines and chemokines. Furthermore, a Cxcl17 −/− mouse developed exacerbated disease in a T cell-dependent model of experimental autoimmune encephalomyelitis (EAE). By 18 days after immunization with myelin oligodendrocyte peptide, only 44% of Cxcl17 −/− mice were still alive vs. 90% for WT mice. During EAE, Cxcl17 −/− mice exhibited higher numbers of lymphoid and myeloid cells in spleen and LNs, whereas they had less myeloid cell infiltration in the CNS. Cxcl17 −/− mice also had higher levels of some inflammatory cytokines in serum, suggesting that they may be involved in the poor survival of these mice. Abnormal T cell function may reflect altered myeloid cell migration, or it could be due to altered T cell development in the thymus. We conclude that CXCL17 is a novel factor regulating T cell homeostasis and function.
AB - CXCL17 is a homeostatic chemokine in the mucosa known to chemoattract dendritic cells and macrophages but can also be expressed elsewhere under inflammatory conditions. Cxcl17 −/− mice have lower numbers of macrophages or dendritic cells in mucosal tissues. CXCL17 is also able to chemoattract suppressor myeloid cells that can recruit regulatory T cells. To explore a possible role of Cxcl17 in T cells, we studied T cell populations from Cxcl17 −/− or wild-type (WT) littermate mice. Cxcl17 −/− mice have higher numbers of CD4 + and CD8 + T cells in spleen and lymph nodes (LNs). Upon activation, they produce higher levels of several proinflammatory cytokines and chemokines. Furthermore, a Cxcl17 −/− mouse developed exacerbated disease in a T cell-dependent model of experimental autoimmune encephalomyelitis (EAE). By 18 days after immunization with myelin oligodendrocyte peptide, only 44% of Cxcl17 −/− mice were still alive vs. 90% for WT mice. During EAE, Cxcl17 −/− mice exhibited higher numbers of lymphoid and myeloid cells in spleen and LNs, whereas they had less myeloid cell infiltration in the CNS. Cxcl17 −/− mice also had higher levels of some inflammatory cytokines in serum, suggesting that they may be involved in the poor survival of these mice. Abnormal T cell function may reflect altered myeloid cell migration, or it could be due to altered T cell development in the thymus. We conclude that CXCL17 is a novel factor regulating T cell homeostasis and function.
KW - CXCL17
KW - T lymphocytes
KW - autoimmunity
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85063004213&partnerID=8YFLogxK
U2 - 10.1002/JLB.3A0918-345RR
DO - 10.1002/JLB.3A0918-345RR
M3 - Artículo
C2 - 30860634
AN - SCOPUS:85063004213
SN - 0741-5400
VL - 105
SP - 1027
EP - 1039
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -