PubMed Health⌕ Search

Biomedical subjects

Shomyseh Sanjabi

Publications and source records attributed to Shomyseh Sanjabi.

5 recordsLinked to original sources
PubMed2006

Transforming growth factor-beta: recent advances on its role in immune tolerance.

Transforming growth factor-beta (TGF-beta) is a key regulator of immune tolerance. In this paper, we will focus on T cells and natural killer (NK) cells, which are directly regulated by TGF-beta in vivo. TGF-beta controls T-cell activation and differentiation, and is involved in the suppressive function and generation of regulatory T cells. Recently, TGF-beta has also been shown to directly inhibit NK cell activity. These studies demonstrate that TGF-beta utilizes multiple mechanisms to ensure immune tolerance, which is critical in a variety of autoimmune and inflammatory disorders. We will also discuss recent advances on the role of TGF-beta in immune-mediated diabetes, inflammatory bowel disease, arthritis, and systemic lupus erythematosus.

Animals↗
PubMed2006

Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms.

The role of transforming growth factor-beta (TGF-beta) in inhibiting T cell functions has been studied with dominant-negative TGF-beta receptor transgenic models; however, the full impact of TGF-beta signaling on T cells and the mechanisms by which TGF-beta signals remain poorly understood. Here we show that mice with T cell-specific deletion of TGF-beta receptor II developed lethal inflammation associated with T cell activation and differentiation. In addition, TGF-beta signaling positively regulated T cell development and homeostasis. Development of CD8+ T cells and NKT cells, maintenance of peripheral Foxp3-expressing regulatory T cells, and survival of CD4+ T cells all depended on TGF-beta signaling. Both T helper 1 (Th1) differentiation and survival of activated CD4+ T cells required T-bet, the TGF-beta-regulated transcription factor, which controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo.

Animals↗
PubMed2006

Transforming growth factor-beta regulation of immune responses.

Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-beta is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-beta inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease.

Animals↗
PubMed2005

A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation.

The NF-kappaB family members p65 (RelA) and c-Rel recognize similar DNA sequences, yet the phenotypes of mutant mice suggest that these proteins regulate distinct sets of genes. Here we demonstrate that 46 unique residues within an 86-residue segment of the Rel homology region (RHR) of c-Rel are responsible for the c-Rel requirement for Il12b gene induction by lipopolysaccharide in bone marrow-derived macrophages. These same residues were responsible for the c-Rel requirement for Il12a induction in dendritic cells, and in both instances, no evidence of c-Rel-specific coactivator interactions was found. Although the residues of c-Rel and p65 that contact specific bases and the DNA backbone within nuclear factor-kappaB (NF-kappaB) recognition sequences are identical, homodimers of c-Rel and of a chimeric p65 protein containing the critical c-Rel residues bound with high affinity to a broader range of NF-kappaB recognition sequences than did wild-type p65 homodimers. These results demonstrate that the unique functions of closely related transcription factor family members can be dictated by differences in the range of DNA sequences recognized at high affinity, despite having similar binding site consensus sequences and DNA contact residues.

Amino Acid Sequence↗