Open AccessMinimal role of interleukin 6 and toll-like receptor 2 and 4 in murine models of immune-mediated bone marrow failure
Author(s) -
Sabrina Solorzano,
Ji-Soo Kim,
Jichun Chen,
Xingmin Feng,
Neal S. Young
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248343
Subject(s) - pancytopenia , bone marrow failure , immunology , tlr2 , immune system , bone marrow , innate immune system , aplastic anemia , biology , acquired immune system , toll like receptor , immunity , haematopoiesis , major histocompatibility complex , immune tolerance , medicine , stem cell , microbiology and biotechnology
Immune aplastic anemia (AA) results from T cell attack on hematopoietic cells, resulting in bone marrow hypocellularity and pancytopenia. Animal models have been successfully developed to study pathophysiological mechanisms in AA. While we have systemically defined the critical components of the adaptive immune response in the pathogenesis of immune marrow failure using this model, the role of innate immunity has not been fully investigated. Here, we demonstrate that lymph node (LN) cells from B6-based donor mice carrying IL-6, TLR2, or TLR4 gene deletions were fully functional in inducing severe pancytopenia and bone marrow failure (BMF) when infused into MHC-mismatched CByB6F1 recipients. Conversely, B6-based recipient mice with IL-6, TLR2, and TLR4 deletion backgrounds were all susceptible to immune-mediated BMF relative to wild-type B6 recipients following infusion of MHC-mismatched LN cells from FVB donors, but the disease appeared more severe in IL-6 deficient mice. We conclude that IL-6, TLR2, and TLR4, molecular elements important in maintenance of normal innate immunity, have limited roles in a murine model of immune-mediated BMF. Rather, adaptive immunity appears to be the major contributor to the animal disease.