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Cxcl17 −/− mice develop exacerbated disease in a T cell‐dependent autoimmune model
Author(s) -
HernándezRuiz Marcela,
Othy Shivashankar,
Herrera Carolina,
Nguyen HongTam,
ArrevillagaBoni Gerardo,
CatalanDibene Jovani,
Cahalan Michael D.,
Zlotnik Albert
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3a0918-345rr
Subject(s) - experimental autoimmune encephalomyelitis , biology , t cell , immunology , myeloid , cd11c , myeloid derived suppressor cell , spleen , cd8 , myelin oligodendrocyte glycoprotein , chemokine , proinflammatory cytokine , dendritic cell , inflammation , microbiology and biotechnology , immune system , suppressor , cancer , gene , phenotype , biochemistry , genetics
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.