Abstract
Chemokines are small secreted proteins functionally involved in the immune system's regulation of lymphocyte migration across numerous mammalian species. Given its growing popularity in immunological models, we investigated the structure and function of chemokine CXCL12 protein in tree shrews. We found that CXCL12 and its receptor CXCR4 in tree shrew had structural similarities to their homologous human proteins. Phylogenetic analysis supports the view that tree shrew is evolutionarily-close to the primates. Our results also showed that the human recombinant CXCL12 protein directly enhanced the migration of tree shrew's lymphocytes in vitro, while AMD3100 enhanced the mobilization of hematopoietic progenitor cells (HPCs) from bone marrow into peripheral blood in tree shrew in vivo. Collectively, these findings suggested that chemokines in tree shrews may play the same or similar roles as those in humans, and that the tree shrew is a viable animal model for studying human immunological diseases.
Highlights
Animal models can effectively demonstrate some of the complexities of both human diseases and the human immune system [1]
Similar to its human homologue, a typical ‘‘KPVSLSYRCPCRFFESH’’ sequence was found at the N-terminal site of the tree shrew CXCL12 protein, and it is this conserved 17 aa domain that directly interacts with the receptor CXCR4 in humans [31]
We found that CXCL12 and CXCR4 were both relatively-high expressed in immune tissues, such as spleen and thymus (Fig. 5A and 5B), implying that CXCL12 and CXCR4 may be involved in some aspect of immunological regulation among tree shrews
Summary
Animal models can effectively demonstrate some of the complexities of both human diseases and the human immune system [1]. While different studies have provided conflicting reports on the origin of the tree shrew as well as its relationship to primates[6,7], tree shrews have still consistently been used to develop experimental models for studying human viruses such as hepatitis A, B, C and H1N1 [8,9,10,11,12] The success of these efforts has largely stemmed from the conceivable similarity between the immune system of the tree shrew and humans (which is not fully characterized, yet) as well as the structural evolution of genes at work in the immune system shared between tree shrews and other primates [6,13]. The step in assessing the viability of the tree shrew model for immunological studies is to gain a more comprehensive understanding of the tree shrews’ molecular and cellular immune mechanisms
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