The integration and control of systemic immune responses depends on the regulated trafficking of lymphocytes. This lymphocyte
“homing” process disperses the immunologic repertoire, directs lymphocyte subsets to the specialized microenvironments that
control their differentiation and regulate their survival, and targets immune effector cells to sites of antigenic or microbial
invasion. Recent advances reveal that the exquisite specificity of lymphocyte homing is determined by combinatorial “decision
processes” involving multistep sequential engagement of adhesion and signaling receptors. These homing-related interactions
are seamlessly integrated into the overall interaction of the lymphocyte with its environment and participate directly in
the control of lymphocyte function, life-span, and population dynamics. In this article a review of the molecular basis of
lymphocyte homing is presented, and mechanisms by which homing physiology regulates the homeostasis of immunologic resources
"It is well known that parenteral vaccination is not very effective in inducing protection against intestinal infections . Recent studies have shown that the main reason for this phenomenon is that B-and T-cell priming in the lymphoid organs of the intestinal mucosa induces the homing receptor constituted by the integrin ␣4␤7 and the chemokine receptor CCR9  . However, these receptors are not induced peripherally, since the DCs present in the intestinal lymphoid organs (and other mucosa, like the upper respiratory track) secrete retinoic acid at the moment of the B-and T-cell priming  . "
"To mount an effective immune response, T and B lymphocytes must migrate into tissue, which depends on the regulated trafficking of lymphocytes . This 'homing' process eventually leads to the recruitment of immune effector cells to sites of antigenic or microbial invasion. "
[Show abstract][Hide abstract] ABSTRACT: A variety of ion channels has been discovered in lymphocytes. RT-PCR and real-time PCR analysis revealed that ALL (acute lymphocytic leukemia) cell lines and human peripheral blood mononuclear cells mainly expressed TTX (tetrodotoxin)-sensitive voltage-gated sodium channels (VGSCs). Expression of VGSC protein was confirmed by western blots and Immunofluorescence. Whole-cell patch-clamp recordings showed that a sub-population (20%) of MOLT-4 cells expressed functional VGSCs, which were TTX-sensitive. Importantly, 2 μM TTX decreased the invasion of Jurkat and MOLT-4 cells ∼90%. These results indicate that the activity of VGSCs could represent a novel mechanism potentiating the invasive capacity of these cells.
Biochemical and Biophysical Research Communications 01/2015; 247(2). DOI:10.1016/j.bbrc.2015.01.103 · 2.30 Impact Factor
"Delineating the specific nuclear receptors governing these events is needed for the refinement of retinoid-based therapies. Since cell adhesion and migration are paramount in immunity, the particular role of retinoids in these processes has been an area of particular interest  . Seminal studies have established that atRA bestows gut homing properties to lymphocytes   . "
[Show abstract][Hide abstract] ABSTRACT: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (a disintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH)(2)D-3, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-alpha receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.
Biochemical and Biophysical Research Communications 10/2014; 454(4). DOI:10.1016/j.bbrc.2014.10.120 · 2.30 Impact Factor
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