Endometriosis in reproductive immunology

PROBLEM: Endometriosis is suggested to represent an autoimmune disorder, but what is the prevalence of autoantibodies to antigens relevant to reproduction? METHOD OF STUDY: The humoral immune response to the women with endometriosis (stage I–II: 261 women; stage III–IV: 62 women) in serum and in peritoneal fluid was investigated compared with 101 healthy women. Enzyme‐linked immunosorbent assay (ELISA) was used in all the women for the detection of seven antiphospholipid antibodies [antiphospholipid antibodies (aPLs) against cardiolipin, L ‐phosphatidyl (ph)‐serine, ph‐glycerol, ph‐inositol, ph‐ethanolamine, phosphatidic (ph)‐acid and against β2‐glycoprotein I] of class IgG, IgA, and IgM. A passive haemmagglutination method and ELISA (BioGen) was used for assessment of antizona pellucida antibodies (aZP), tray agglutination test (TAT) and indirect mixed anti‐imunoglobulin reaction test (MAR‐test) for the determination of sperm antibody levels. RESULTS: Endometriosis I–II were associated with higher serum and peritoneal fluid levels of aPLs against inositol, cardiolipin, ethanolamine, and β2‐glycoprotein I. Forty percent of patients were positive for aZPA. CONCLUSIONS: Patients with lesions of endometriosis stage I–II had more autoantibodies than those with stage III–IV, and may be immunologically more active. This result may be significant for future treatments such as in vitro fertilization and embryo transfer.     

Peroxisome proliferator-activated receptors: new players in the field of reproduction

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear hormone receptor superfamily. Synthetic ligands to one family member, PPARgamma, are currently widely used as treatment for chronic diseases such as diabetes type II and other insulin resistances, e.g. as seen in polycystic ovary syndrome (PCOS). Moreover, novel approaches employing knock-out mice demonstrated that PPARgamma seems to play a key role in placental and fetal development. This review describes recent insights into the role of PPARs in human reproduction with specific reference to infertility, placental maturation and fetal development as well as disturbed pregnancy. Further, we highlight the current knowledge on synthetic ligands to PPARgamma used as a treatment in women with PCOS.     

Toll-like receptors: new players in myocardial ischemia/reperfusion injury

Innate immune and inflammatory responses have been implicated in myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate immunity and inflammatory response are involved in myocardial I/R have not been elucidated completely. Recent studies highlight the role of Toll-like receptors (TLRs) in the induction of innate immune and inflammatory responses. Growing evidence has demonstrated that TLRs play a critical role in myocardial I/R injury. Specifically, deficiency of TLR4 protects the myocardium from ischemic injury, whereas modulation of TLR2 induces cardioprotection against ischemic insult. Importantly, cardioprotection induced by modulation of TLRs involves activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting that there is a crosstalk between TLRs and PI3K/Akt signaling pathways. In addition, TLRs also associate with other coreceptors, such as macrophage scavenger receptors in the recognition of their ligands. TLRs are also involved in the induction of angiogenesis, modulation of stem cell function, and expression of microRNA, which are currently important topic areas in myocardial I/R. Understanding how TLRs contribute to myocardial I/R injury could provide basic scientific knowledge for the development of new therapeutic approaches for the treatment and management of patients with heart attack.     

Chemokine receptors in inflammation: an overview

Chemokine receptors play a key role in directing the migration of inflammatory cells into various injured or infected organs. However, migration of inflammatory cells into tissues can in itself be a cause and amplifier of tissue damage and disease, particularly in chronic autoimmune or allergic disorders. On this basis, much effort is currently devoted at the identification of molecular signals regulating the recruitment of inflammatory cells into tissues and at developing novel strategies to inhibit discrete pathways in this process. Great progress has recently been made in identification of a number of chemokine receptors involved in the process of leukocyte migration. The challenge is now to elucidate the specific contribution and involvement of the different receptors in distinct inflammatory processes and diseases and to prove that interference with any of these pathways may lead to development of novel therapeutics.     

Controversies in reproductive immunology.

Nine areas of current controversy in the field of immunology of reproduction have been selected for discussion: (1) do antisperm antibodies cause infertility; (2) does cell mediated immunity cause infertility; (3) do antibodies cause spontaneous abortion; (4) is abortion due to rejection of the "fetal allograft"; (5) is altered antigen expression crucial for survival of the "fetal allograft"; (6) is abortion mediated by graft rejection mechanisms; (7) does locoregional suppression prevent abortion; (8) does immunization to prevent abortion and promote pregnancy act via immunotropism and cytokine cross-talk; (9) do immune responses prevent spontaneous abortion in humans? The reasons for debate and uncertainty are reviewed and current data considered in an attempt to arrive at the most likely answer to each question. Directions for future research are proposed where appropriate.     

Chemokine receptors in allergic diseases

Under homeostatic conditions, as well as in various diseases, leukocyte migration is a crucial issue for the immune system that is mainly organized through the activation of bone marrow‐derived cells in various tissues. Immune cell trafficking is orchestrated by a family of small proteins called chemokines. Leukocytes express cell‐surface receptors that bind to chemokines and trigger transendothelial migration. Most allergic diseases, such as asthma, rhinitis, food allergies, and atopic dermatitis, are generally classified by the tissue rather than the type of inflammation, making the chemokine/chemokine receptor system a key point of the immune response. Moreover, because small antagonists can easily block such receptors, various molecules have been developed to suppress the recruitment of immune cells during allergic reactions, representing potential new drugs for allergies. We review the chemokines and chemokine receptors that are important in asthma, food allergies, and atopic dermatitis and their respectively developed antagonists.     

Chemokine receptors and transplantation

A complex process including both the innate and acquired immune responses results in allograft rejection.Somechemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but alsoin facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage ofthe aliogeneic response.This review focuses on the impact of these chemoattractant proteins on transplant outcomeand novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokinereceptors and/or their ligands.Cellular & Molecular Immunology.2005;2(5):343-349.     

Chemokine receptors: understanding their role in asthmatic disease

The incidence, prevalence, and severity of asthma have been increasing steadily in recent years. Prophylactic treatment of this disease and of episodic asthmatic flares is aimed at preventing excessive inflammation in lung tissue and airways. Because chemokines and chemokine receptors are critical mediators of leukocyte trafficking and recruitment, there is the potential to pharmaceutically target these proteins to regulate inflammation. Asthma-associated inflammation is characterized by the infiltration of eosinophils and T helper type 2 cells. Early studies investigated the role of chemokine receptors, which have been shown to predominate on these cell populations.     

Chemokine receptors and molecular mimicry

Chemokines are small pro-inflammatory peptides that are best known for their leukocyte-chemoattractant activity. The cloned leukocyte chemokine receptors, interleukin 8 receptor (IL-8R) types A and B and the macrophage inflammatory protein 1α (MIP-1α/RANTES receptor, are related by sequence and chemokine binding to two herpesvirus products, and to the Duffy antigen that mediates erythrocyte invasion by the malaria-causingg parasite H smodium vivax. Here, Sunil Abuja, Ji-Liang Gao and Philip Murphy suggest that in addition to the activation of leukocytes, chemokines may be important in the function of erythrocytes and, through molecular mimicry, in microbial pathogenesis.     

Face-offs in reproductive immunology: the Montreal forum meeting report

The combined 12th International Congress of Immunology (ICI) and the 4th Annual Conference of the Federation of Clinical Immunological Societies (FOCIS) was held in Montreal, Canada July 18-23, 2004 and attracted over 6000 immunologists and almost 4000 abstracts. The host society, the Canadian Society for Immunology (CSI) spent many years in preparation for this large meeting and encouraged its members to propose topics for symposia and mini-symposia and to sponsor satellite meetings. With sponsorship of CSI; the Canadian Institutes of Health Research; the University of Guelph, Guelph, ON; Queen's University, Kingston, ON; McGill University, Montreal, QU, Canada; and the American Society for Reproductive Immunology, a focused, highly successful, one day satellite meeting on human uterine immunology was held. The highlights of the presentations and discussions are reported.     

Mucosal immunology: new frontiers

Mucosal immunology is one of the most rapidly developing and exciting fields of immunological research. A recent meeting discussed advances in the fundamental knowledge of this area, and reviewed possibilities for its clinical application.     

Chemokine receptors in lymphoid organ homeostasis.

Leukocytes respond to complex patterns of chemoattractant cytokine (chemokine) gradients that guide them to their destinations in secondary lymphoid organs. This directed movement of multiple cell types requires the choreographed expression of specific G-protein-coupled chemokine receptors and both positive and negative regulation of the signal transduction pathways emanating from them.     

Chemokine receptors as biomarkers in multiple sclerosis

Leukocyte infiltrates characterize tissue inflammation and are thought to be integral in the pathogenesis of multiple sclerosis (MS). This attribute underlines the importance of understanding mechanisms of leukocyte migration. Chemokines are secreted proteins which govern leukocyte trafficking into targeted organs. Chemokine receptors (CKR) are differentially expressed on leukocytes and their modulation is a potential target for MS disease modifying therapies. Chemokines and their receptors are also potential biomarkers of both disease activity and response to treatment. We describe the fluctuations in CKR expression on peripheral leukocytes in a group of MS patients followed longitudinally for up to 36 months. We observed little fluctuation in CKR expression within each patient over time, despite considerable variability in CKR expression between patients. These observations suggest that individual patients have a CKR set point, and this set point varies from one patient to another. Evaluation of chemokines or chemokine receptors as biomarkers in MS will need to account for this individual variability in CKR expression.     

趋化因子受体对免疫应答的调节及其治疗意义

趋化因子 (ｃｈｅｍｏｋｉｎｅｓ)是一类对血细胞迁移和聚集有调节作用的小分子多肽 ,根据多肽链一级结构中半胱氨酸 (ｃｙｓｔｅｉｎｅ ,ｃｙｓ)残基的位置 ,可分为 4个亚族 :ＣＣ、ＣＸＣ、Ｃ和ＣＸ3Ｃ。其活性的发挥有赖其相应受体 ,即七次跨膜受体 (Ｇ蛋白偶联受体 )的存在 ,后者在粒细胞、单核 /巨噬细胞、Ｔ细胞膜上有不同种类的表达 ,因此众多的趋化因子对免疫细胞的作用呈现了相应的选择性。天然 (ｎａｉｖｅ)Ｔ细胞迁出胸腺后在外周血及周围淋巴器官内循环 ,与成熟的抗原递呈细胞 (ａｎｔｉｇｅｎ -ｐｒｅｓｅｎｔｉｎｇｃｅｌｌ,…