From the ECM to the Cytoskeleton and Back: How Integrins Orchestrate T Cell Action

T lymphocytes constitute a highly dynamic tissue type. During the course of their lives, they travel through a variety of physiological environments and experience a multitude of interactions with extracellular matrix components and other cells. In order to do this, they must receive many environmental cues, and translate these signals into the appropriate biological actions. Particularly dramatic are the cytoskeletal shape changes a T cell must undergo during the processes of leaving the bloodstream, migrating through tissues, and encountering antigen. In this review, we highlight the role of integrins in providing a link between the extracellular environment and cytoskeletal regulation and how these receptors help to orchestrate T cell migration and antigen recognition

Histamine and cis-urocanic acid augment tumor necrosis factor-alpha mediated induction of keratinocyte intercellular adhesion molecule-1 expression

Early cellular and molecular events in inflamed skin include the active participation of epidermal keratinocytes (KCs) and dermal mast cells which can produce diffusible mediators such as tumor necrosis factor-alpha (TNF-Α), histamine, and urocanic acid (UCA). Rapid induction of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by KCs is observed following a highly diverse array of stimuli which can provoke both irritant, inflammatory, as well as allergic and immune reactions. To determine if the aforementioned mediators could interact in either an additive or synergistic fashion with each other, cultured KCs were exposed to these mediators alone and in combination, and the degree of ICAM-1 mRNA and protein quantitated. Whereas histamine or cis-UCA alone only weakly induced KC ICAM-1, when they were combined with TNF-Α, significant augmentation was observed by Northern blot hybridization studies, immunostaining, and FACS analysis. Other histamine derivatives such as L-histidine, 1-methylhistidine, 3-methylhistidine, or all-trans-UCA had no effect. Histamine pretreatment did not affect cell surface high affinity TNF-Α receptors, as determined by ligand binding and immunodetection, and did not induce KC TNF-Α production. The KC histamine receptor was also characterized and found not to be influenced by TNF-Α, cis-UCA, all-trans-UCA, or diphenyhydramine (an H 1 antagonist), but it was inhibited by cimetidine (an H 2 antagonist). These results demonstrate that 1) KCs can be induced to express ICAM-1 by exposure to histamine and cis-UCA, 2) histamine and cis-UCA can also augment TNF-Α inducible ICAM-1 mRNA and cell surface protein expression, 3) this augmentation does not directly involve changes in KC TNF-Α receptor number, affinity, or TNF-Α production and, 4) KCs possess a type 2 histamine receptor which is not the photoreceptor for UCA. These findings highlight the potential for cross-talk between molecules produced by resident cutaneous cell types above (i.e., KCs) and below (i.e., mast cells) the epidermal basement membrane zone. These cells and their mediators can cooperate to respond to either exogenous or endogenous stimuli leading to rapid and strong KC ICAM-1 expression. Such induction of this important adhesion molecule by KCs ensures the retention of T lymphocytes necessary to participate in the maintenance of cutaneous immunohomeostasis. © 1993 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49885/1/1041560218_ftp.pd

Lymphocyte interactions with endothelial cells

Adhesion of lymphocytes to endothelium is vital to lymphocyte migration into lymphoid tissue and into inflammatory sites. In this review, Yoji Shimizu and colleagues identify the molecules that mediate lymphocyte-endothelial cell adhesion, describe the underlying principles of lymphocyte migration, and discuss a model of the sequence of events that allow a lymphocyte to successfully attach to endothelium and migrate into the surrounding tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30298/1/0000700.pd

Roles of multiple accessory molecules in T-cell activation

Accessory molecules expressed on T cells can mediate adhesion between T cells and other cells, or the extracellular matrix. The same T-cell accessory molecules participate in a dialogue with their ligands (counter-receptors) on the antigen-presenting cells, and elicit signals that determine the specifics of activation and subsequent differentiation of the T cells and antigen-presenting cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29305/1/0000368.pd

A functional genomics tool for the Pacific bluefin tuna: Development of a 44K oligonucleotide microarray from whole-genome sequencing data for global transcriptome analysis

AbstractBluefin tunas are one of the most important fishery resources worldwide. Because of high market values, bluefin tuna farming has been rapidly growing during recent years. At present, the most common form of the tuna farming is based on the stocking of wild-caught fish. Therefore, concerns have been raised about the negative impact of the tuna farming on wild stocks. Recently, the Pacific bluefin tuna (PBT), Thunnus orientalis, has succeeded in completing the reproduction cycle under aquaculture conditions, but production bottlenecks remain to be solved because of very little biological information on bluefin tunas. Functional genomics approaches promise to rapidly increase our knowledge on biological processes in the bluefin tuna. Here, we describe the development of the first 44K PBT oligonucleotide microarray (oligo-array), based on whole-genome shotgun (WGS) sequencing and large-scale expressed sequence tags (ESTs) data. In addition, we also introduce an initial 44K PBT oligo-array experiment using in vitro grown peripheral blood leukocytes (PBLs) stimulated with immunostimulants such as lipopolysaccharide (LPS: a cell wall component of Gram-negative bacteria) or polyinosinic:polycytidylic acid (poly I:C: a synthetic mimic of viral infection). This pilot 44K PBT oligo-array analysis successfully addressed distinct immune processes between LPS- and poly I:C- stimulated PBLs. Thus, we expect that this oligo-array will provide an excellent opportunity to analyze global gene expression profiles for a better understanding of diseases and stress, as well as for reproduction, development and influence of nutrition on tuna aquaculture production

An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function

NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication