Showing papers on "MERTK published in 2007"

Macrophages and Dendritic Cells Use Different Axl/Mertk/Tyro3 Receptors in Clearance of Apoptotic Cells

Abstract: The clearance of apoptotic cells is important for regulating tissue homeostasis, inflammation, and autoimmune responses. The absence of receptor tyrosine kinases (Axl, Mertk, and Tyro3) results in widespread accumulation of apoptotic cells and autoantibody production in mice. In this report, we examine the function of the three family members in apoptotic cell clearance by different phagocytic cell types. Mertk elimination nearly abolished macrophage apoptotic cell phagocytosis; elimination of Axl, Tyro3, or both, reduced macrophage phagocytosis by approximately half, indicating that these also play a role. In contrast, apoptotic cell clearance in splenic and bone marrow-derived dendritic cells (DCs) is prolonged compared with macrophages and relied primarily on Axl and Tyro3. The slower ingestion may be due to lower DC expression of Axl and Tyro3 or absence of GAS6 expression, a known ligand for this receptor family. In vivo, phagocytosis of apoptotic material by retinal epithelial cells required Mertk. Unlike macrophages, there did not appear to be any role for Axl or Tyro3 in retinal homeostasis. Likewise, clearance of apoptotic thymocytes in vivo was dramatically reduced in mertk(kd) mice, but was normal in axl/tyro3(-/-) mice. Thus, cell and organ type specificity is clearly delineated, with DCs relying on Axl and Tyro3, retina and thymus requiring Mertk, and macrophages exhibiting an interaction that involves all three family members. Surprisingly, in macrophages, tyrosine phosphorylation of Mertk in response to apoptotic cells is markedly diminished from axl/tyro3(-/-) mice, suggesting that the interactions of these receptors by heterodimerization may be important in some cells.

MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients

Abstract: Objective. The MER receptor tyrosine kinase (MERTK) gene is critical for the efficient clearance of apoptotic cells and has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the genetic polymorphisms in MERTK to evaluate it as a potential candidate gene for a host genetic study of SLE and clinical manifestations in patients with SLE. Methods. By resequencing the coding and flanking regions of the MERTK gene in 24 unrelated Koreans, 37 polymorphisms were identified. Based on gene position, minor allele frequency and inter-single-nucleotide polymorphism (SNP) linkage disequilibrium, six of these polymorphisms were selected for subsequent genotyping and association analysis with the risk of SLE and haematological disorders in 350 Korean SLE patients and 330 controls. Results. Although no significant associations with the risk of SLE were found, logistic regression analyses revealed that variants þ465C > G (P ¼ 0.05) and þ130215insdelT (P ¼ 0.0005) were significantly associated with decreased risk of leucopenia in SLE patients. Further, þ465C > G, þ95616G > A, þ123157A > G and the haplotype ht1 also showed significant associations (P ¼ 0.006–0.05) with a decreased risk of lymphopenia in SLE patients. Conclusion. Our findings suggest that polymorphisms in MERTK might be one of the genetic risk factors for presenting leucopenia and lymphopenia in SLE patients.

The role of MerTK and BAFF in dendritic cell-B cell interactions

Abstract: Paul Reid Gohlke: The Role of MerTK and BAFF in Dendritic Cell-B cell Interactions (Under the direction of Dr. Glenn K. Matsushima) Autoimmune disease occurs when the system of cells and molecules designed to protect the host from invading pathogens directs itself towards attacking the host. The development of autoimmunity involves the participation of several cell types each with a distinct role in disease pathogenesis. Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which autoreactive B cells produce antibodies directed against ubiquitous components of the cell nucleus. Although B cells are the effector cell type in this process, specific genetic deletions in mouse models have shown that improper function of the non-B cell components of the immune system can be sufficient to coerce otherwise tolerant B cells into becoming autoantibody-producing cells. Mice lacking a functional version of the receptor tyrosine kinase MerTK (mertk mice) are one such model. As in SLE, mertk mice develop autoantibodies to antigens normally found in the cell nucleus such as dsDNA, ssDNA, chromatin, and Sm. While MerTK is not normally expressed by B or T cells, it is expressed by myeloid-lineage cells such as dendritic cells and macrophage. Since dendritic cells are known to both, present antigen to B cells, as well as produce the cytokine BAFF, we decided to investigate the possibility that dendritic cells from mertk mice are facilitators of B cell autoimmunity. Our experiments demonstrate that MerTK functions to restrict spontaneous BAFF