Several important events occur at the maternal–fetal interface, including generation of maternal–fetal tolerance, remodeling of the uterine smooth muscle and its spiral arteries and glands, and placental construction. Fetal-derived extravillous trophoblasts come in direct contact with maternal decidual leukocytes. Macrophages represent ~20% of the leukocytes at this interface. In this study, two distinct subsets of CD14+ decidual macrophages (dMϕs) are found to be present in first-trimester decidual tissue, CD11cHI and CD11cLO. Gene expression analysis by RNA microarray revealed that 379 probes were differentially expressed between these two populations. Analysis of the two subsets revealed several clusters of coregulated genes that suggest distinct functions for these subsets in tissue remodeling, growth, and development. CD11cHI dMϕs express genes associated with lipid metabolism and inflammation, whereas CD11cLO dMϕs express genes associated with extracellular matrix formation, muscle regulation, and tissue growth. The CD11cHI dMϕs also differ from CD11cLO dMϕs in their ability to process protein Ag and are likely to be the major APCs in the decidua. Moreover, these populations each secrete both proinflammatory and anti-inflammatory cytokines that may contribute to the balance that establishes fetal–maternal tolerance. Thus, they do not fit the conventional M1/M2 categorization.

Human decidual CD14 ؉ macrophages and CD56 ؉ NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class Ib protein that is expressed on extravillous trophoblasts), LILRB1 on CD14 ؉ macrophages and KIR2DL4 on CD56 ؉ NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNF␣ detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.IL-6 ͉ IL-8 ͉ pregnancy ͉ trophoblast ͉ VEGF

Summary Colonial marine invertebrates, such as sponges, corals, bryozoans, and ascidians, often live in densely-populated communities where they encounter other members of their species as they grow over their substratum. Such encounters typically lead to a natural histocompatibility response in which colonies either fuse to become a single, chimeric colony or reject and aggressively compete for space. These allorecognition phenomena mediate intraspecific competition [1–3], support allotypic diversity [4], control the level at which selection acts [5–8], and resemble allogeneic interactions in pregnancy and transplantation [9–12]. Despite the ubiquity of allorecognition in colonial phyla, however, its molecular basis has not been identified beyond what is currently known about histocompatibility in vertebrates and protochordates. We positionally cloned an allorecognition gene using inbred strains of the cnidarian, Hydractinia symbiolongicarpus, which is a model system for the study of invertebrate allorecognition. The gene identified encodes a putative transmembrane receptor expressed in all tissues capable of allorecognition that is highly polymorphic and predicts allorecognition responses in laboratory and field-derived strains. This study reveals that a previously undescribed hypervariable molecule bearing three extracellular domains with greatest sequence similarity to the immunoglobulin superfamily is an allodeterminant in a lower metazoan.

Summary Allorecognition, the ability to discriminate between self and non-self, is ubiquitous amongst colonial metazoans and widespread amongst aclonal taxa [1–3]. Genetic models for the study of allorecognition have been developed in the jawed vertebrates [4], invertebrate chordate Botryllus [5, 6], and cnidarian Hydractinia [7]. In Botryllus, two genes contribute to the histocompatibility response, FuHC [5, 8] and fester [6]. In the cnidarian Hydractinia, one of the two known allorecognition loci, alr2, has been isolated [7] and a second linked locus, alr1, has been mapped to the same chromosomal region, called the allorecognition complex (ARC) [9, 10]. Here we isolate alr1 by positional cloning and report it to encode a transmembrane receptor protein with two hypervariable extracellular regions similar to immunoglobulin (Ig)-like domains. Variation in the extracellular domain largely predicts fusibility within and between laboratory strains and wild-type isolates. Alr1 was found embedded in a family of immunoglobulin superfamily-like (IgSF) genes, thus establishing that the ARC histocompatibility complex is an invertebrate IgSF-like gene complex.

We have developed defined genetic lines of the hydroid Hydractinia symbiolongicarpus and confirmed earlier results showing that allorecognition is controlled by a single chromosomal region within these lines. In a large backcross population, we detected recombinants that display a fusibility phenotype distinct from typical fusion and rejection. We show that this transitory fusion phenotype segregates in a fashion expected of a single Mendelian trait, establishing that the chromosomal interval contains at least two genes that interact to determine fusibility. Using bulked segregant analysis, we have identified amplified fragment length polymorphisms (AFLP) cosegregating with fusibility, used these markers to independently confirm linkage of the two loci, and constructed a 3.4-cM map of an invertebrate histocompatibility complex.T HE hydroid Hydractinia has a long been a favored quently applied a conventional incross/intercross/backcross analysis. Within these defined genetic lines, Hymodel in efforts to understand invertebrate allorecognition (von Hauenschild 1954(von Hauenschild , 1956 Mü ller 1964; dractinia allorecognition segregated as a one-locus trait with codominant expression of alleles, such that two Buss et al. 1984;Mü ller et al. 1987;Lange et al. 1989Lange et al. , 1992; Buss and Grosberg 1990; Shenk and Buss 1991; colonies fuse if they share at least one allele. Grosberg et al. 1996; Mokady and Buss 1996). Colonies, We here report the further development of these inwhich often encrust the shells of hermit crabs, grow by bred and congenic lines and confirm, with an expanded elongation and branching of stolons. When two or more population, that segregation of fusibility follows singlelarvae recruit to the same substratum, stolons of differlocus codominant Mendelian expectations. A fusibility ent colonies may eventually come into contact. Close phenotype first observed by von Hauenschild (1954, proximity of an approaching stolon induces the produc-1956), in which interacting colonies initially fuse only tion of a new stolon tip along the flank of the stolon to later separate, appeared at low frequencies in this being approached. If the two colonies are histocompaticross. We report a series of crosses that establish that ble, the two tips will first adhere, and then fuse, establishthe transitory fusion (TF) phenotype itself behaves as ing functional gastrovascular continuity and a permaa single Mendelian trait linked to the original allorecognent genetic chimera. In contrast, tips of incompatible nition locus. Moreover, we show that this TF phenotype colonies fail to adhere to one another, but instead swell is readily detected in only one of the two conventional with the migration of nematocysts, which discharge to fusion assays. Finally, we use bulked segregant analysis effect tissue damage.to identify molecular markers linked to the interval and The transmission genetics of allorecognition in Hyreport the use of these markers to construct a genetic dractinia were first addressed in the mid-19...