Page 155 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

often mistaken for autoimmune disease[64]. Thus, for the treatment of autoimmune disease, immunosuppression in lymphocyte compartment without concomitant innate immunosuppression appears much more attractive as the blank immunosuppression, such as occurs with, for instance, steroid treatment, the mainstay of current treatment of autoimmune disease. Apparently, as microgravity does not seem to negatively affect neutrophil-dependent immunity, identifying the targets of microgravity on human immunity may prove exceedingly useful for identifying such targets.
Altered signal transduction is important for microgravity effects on immune function
Thus the available evidence suggests that different cell types alter their characteristics during microgravity and that these effects cell-autonomous, i.e., they do not majorly involve differences in the extracellular milieu, but involve an altered intracellular reaction to an extracellular stimulus. The most straightforward fashion in which such an effect could occur is that the interaction between extracellular cues and their corresponding receptors is disturbed during microgravity. This, however, does not seem to be the case, for instance, the binding of Con-A to T cell membrane glycoproteins remains unchanged, and patching and capping are only minimally retarded at 0×g[65]. Although not involving immunologically relevant cells, also the observation that the otherwise microgravity-sensitive EGF response in A431 cells does not require altered EGF receptor clustering on the surface of A431 cells supports this notion[66]. Thus it seems that subsequent intracellular biochemistry is the target here. Support for this idea comes from the observation that induction of early genes (i.e. genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli and seem to serve an alarm bell for the nuclear machinery that alteration in its transcriptional programming are imminent and form the first nuclear reaction to an extracellular stimulus)[34, 32, 33], apparently limiting the possible interaction points of microgravity with immunity with the direct signaling machinery associated with transmitting the extracellular signals to the nucleus and possibly not necessarily involving altered reactions to secondary nucleus-derived signals.
Altered signal transduction in immunological cells may be dependent on diminished Rac activation
The nature of the effects of microgravity on cellular signal transduction remains unclear. It is tempting to speculate that these results may involve alterations in signaling
Health from above?
Health from above?
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