The unique regulation and patterning of B7 family molecules

in the placenta, together SCH772984 nmr with emerging empirical data, suggests that these proteins may play an important role in shaping the milieu of the local maternal–fetal environment. In addition, the nature of the costimulatory and co-inhibitory signals B7 family members provide will also influence the outcome of the interaction of maternal lymphocytes with fetal antigen in lymphoid tissues. From the experimental data in humans, we can infer that B7 family proteins could function in at least three distinct capacities (Fig. 4). First, the B7 expressing cells in pregnancy that could function as APCs, i.e., those that express both B7 molecules and MHC, may directly influence T-cell activation and effector functions by delivering a positive or negative costimulatory signal in conjunction with TCR stimulation. Second, trophoblast cells that repress MHC might affect lymphocytes through B7/CD28 family molecules

in trans. Finally, B7 molecules on either decidual APCs or trophoblast cells may backsignal toward the B7-expressing cell and influence the local immune environment through induced expression of immunosuppressive RXDX-106 molecular weight factors independently of their effects on T cells. Thus, in determining the functions of these key regulators of the immune system, there is a need to think ‘outside the box’ when considering B7 family molecules during pregnancy. The authors thank Sarika Kshirsagar and Joseph

Juscius for their technical contributions and Stanton Fernald (University of Kansas Interdisciplinary Center for Male Contraceptive Research & Drug Development Imaging Core) for assistance with images. A.L.P. is supported by NIH training grant T32HD007455. This work is supported by NIH grants R01 HD045611, P01 HD049480, and P20 RR16475. “
“Toll-like receptors (TLRs) play a central role in the innate immune response, recognizing a variety of molecular structures characteristic of pathogens. Although TLR4, together with its co-receptor MD-2, recognize bacterial lipopolysaccharide (LPS) and therefore Gram-negative bacterial infections, it also plays a key role Thiamet G in many other pathophysiological processes, including sterile inflammation and viral infection. Specifically, numerous endogenous agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have been reported. Direct activation of a single receptor by such a range of molecular signals is very difficult to explain from a structural and mechanistic point of view. It is likely that only a subset of these directly activate the TLR4-MD2 complex. We propose three postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators.