Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.Following the well-known epidemiological study conducted in Northwest Greenland in the 1970s (Dyerberg et al., 1978), several clinical assessments have indicated that a diet rich in ω3 polyunsaturated fatty acids (PUFAs) has beneficial effects in various inflammatory diseases, including asthma, psoriasis, inflammatory bowel diseases, and rheumatoid arthritis (Horrobin, 1987). Although it remains unclear how ω3 PUFAs exert such antiinflammatory effects, recent studies have identified several derivatives of ω3 PUFAs that possess strong antiinflammatory effects (Serhan et al., 2008; Tull et al., 2009). Resolvin E1 (RvE1) is one such antiinflammatory lipid mediator.RvE1 is known to exert its actions through two receptors, BLT1 and ChemR23 (Arita et al., 2007). RvE1 binds to BLT1, a G protein–coupled receptor for leukotriene B4 (LTB4), and inhibits BLT1 signals (Arita et al., 2007). In addition, RvE1 exhibits an agonistic activity toward ChemR23 (Arita et al., 2007), a G protein–coupled receptor for chemerin. The antiinflammatory effects of RvE1 have been demonstrated in acute innate immune inflammation, such as peritonitis (Arita et al., 2007) and colitis (Arita et al., 2005b). In these models, RvE1 exerted its antiinflammatory effects by inhibiting neutrophil infiltration into the inflammatory foci through a blockade of LTB4-BLT1 signaling in neutrophils (Haas-Stapleton et al., 2007). In contrast, few studies have been conducted on the effect of RvE1 on acquired immune responses, in which DCs and T cells play major roles in the development. In these studies, the attenuated cytokine production, such as IL-12 and IL-23, from DCs is considered as the major mechanism by which RvE1 exerts the antiinflammatory effects (Arita et al., 2005a; Haworth et al., 2008). However, the effect of RvE1 on DC motility has not been investigated in the context of acquired immunity.In the peripheral tissues such as the skin, DCs migrate in an amoeboid movement that requires actin polymerization via activation of the Rho family of small GTPases, such as Cdc42, Rac, and Rho A (Lämmermann and Germain, 2014). In acquired immunity such as contact hypersensitivity (CHS), upon uptake of foreign antigens, DCs migrate to the draining LNs (dLNs) via lymphatic vessels to establish sensitization by inducing the antigen-specific T cell differentiation (Honda et al., 2013). In elicitation, DC migration to form DC–T cell clustering is required for efficient antigen presentation in situ (Natsuaki et al., 2014). Thus, active DC motility is an essential factor for acquired immunity.In this study, we investigated the effects and underlying mechanisms of RvE1 on DC motility using a CHS model, which is a prototype of delayed-type hypersensitivity in the skin mediated by IFN-γ (Mori et al., 2008; Honda et al., 2013). RvE1 inhibited cutaneous DC migration into the dLNs and suppressed antigen-specific T cell induction in the sensitization phase. In addition, live imaging analysis revealed that RvE1 inhibited cutaneous DC motility and cluster formation in the skin, which subsequently attenuated activation of effector T cells in the skin in the elicitation phase of CHS. Intriguingly, LTB4 induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. These results suggest that RvE1 exerts its antiinflammatory effects in cutaneous acquired immunity by inhibiting DC motility, possibly through an LTB4-BLT1 signaling blockade.     

First report of Kudoa species in the somatic muscle of the Japanese parrotfish Calotomus japonicus (Scaridae) and a description of Kudoa igami,n. sp. (Myxozoa: Multivalvulida)

Three species of the Kudoid parasite (Myxozoa: Multivalvulida) were observed in the somatic muscle of Japanese parrotfish Calotomus japonicus caught off the coast of western Japan. All three species formed pseudocysts in myofibers and caused subclinical infections. The three Kudoa species were distinguished by spore morphology, as well as their 18S and 28S rDNA sequences. We identified a previously undescribed taxa Kudoa igami n. sp. with spores that were stellate with rounded peripheral edges and five to six polar capsules (prevalence 29.3 %). Kudoa igami n. sp. were morphologically most similar to Kudoa neothunni but were distinguishable by a more rounded shape in the apical view. Molecular analyses demonstrated that the K. igami n. sp. is closely related to Kudoa thalassomi; however, the similarity in the 28S rDNA sequence was <96 % and the spore morphology was different. We found Kudoa thalassomi in one sample (prevalence 2.4 %), which is a new host and geographical record for this species. Kudoa lateolabracis, which causes postmortem myoliquefaction in Chinese sea bass Lateolabrax sp. and olive flounder Paralichthys olivaceus was found in Japanese parrotfish (prevalence 41.5 %) for the first time, but did not cause myoliquefaction. We also expanded the host record for the brain-infecting Kudoa yasunagai (prevalence 94.1 %). In addition, an unidentified microsporidia was observed in the somatic muscle (prevalence 23.3 %).     

Retrospective analysis of progression to multiple myeloma or related disorders in 114 patients with monoclonal gammopathy of undetermined significance in a single institute

In 114 patients with monoclonal gammopathy of undetermined significance (MGUS) followed-up in Tachikawa Sougo hospital, we retrospectively analyzed progression of their disease to multiple myeloma (MM) or related disorders. The analysis was based on a total of 1,170 person-years of follow-up in a cohort with a median age at diagnosis of MGUS of 68 years 3 months, and with a median follow-up period of 9 years 5 months. Of these 114 patients, 13 (11%) showed progression to MM or related disorders with a median time to progression of 9 years 4 months; and the median age of these 13 patients was 78 years 8 months. The cumulative hazard ratio of progression at 5, 10, 15, and 20 years after diagnosis was 3.0%, 9.0%, 11.4%, and 32.1%, respectively. The risk of progression of MGUS to MM or related disorders in Japanese patients was as high as in Western patients studied previously, demonstrating that MGUS should be carefully monitored as a preneoplastic condition.     

The efficacy of continuous subcostal transversus abdominis plane block for analgesia after living liver donation: a retrospective study

Purpose

Postoperative pain management for living liver donors has become a major concern as a result of the increasing number of living liver donations. Transversus abdominis plane (TAP) block has been known to provide effective analgesia for abdominal surgery. The aim of this study was to evaluate the efficacy of ultrasound-guided continuous subcostal TAP block as a part of a multimodal analgesic regimen in comparison with conventional intravenous (IV) fentanyl-based analgesia in living liver donors.

Methods

Thirty-two donors were retrospectively classified into either the continuous subcostal TAP block group (TAP group) or the IV fentanyl-based analgesia group (control group). TAP group donors received bilateral continuous subcostal TAP infusion of 0.125 % levobupivacaine at 6 ml/h. Control group donors did not receive any neural blockade.

Results

Cumulative fentanyl consumption was significantly lower in the TAP group for 48 h (P < 0.01) as compared to the control group. Further, the donors in the TAP group had significantly lower incidence of nausea and vomiting during 24–48 h postoperatively (P < 0.01) and fewer delays in the initiation of oral intake than those in the control group (P = 0.02).

Conclusions

In conclusion, continuous subcostal TAP block provided an effective opioid-sparing analgesia for living liver donors.