Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responses.

Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their phenotypes and ability to prime and induce the differentiation of naive CD4(+) T cells into effector cells in vitro and in vivo. We found that K/BxNsf PCs had lower levels of the Ag presentation machinery and costimulators than K/BxN PCs, and also a lower CD4(+) T cell priming capacity. Autoantigen-pulsed K/BxNsf PCs selectively polarized cognate CD4(+) T cells toward the expression of molecules necessary for Tfh development and function. As a result, the K/BxNsf PC-primed CD4(+) T cells were more effective in stimulating B cells to produce autoantigen-specific IgGs than K/BxN PCs or even dendritic cells. Adoptive transfer of K/BxNsf PCs, but not K/BxN PCs, to K/BxN mice increased numbers of Tfh cells in draining lymph nodes. These results propose that abnormal accumulation of LLPCs in the spleen of autoimmune models drives the differentiation of autoantigen-primed CD4(+) T cells to Tfh cells. This positive feedback loop between splenic LLPCs and Tfh cells may contribute to the persistence of humoral autoimmunity.

"Fat Brook" in the Popliteal Fossa: Cadaveric and Clinical Investigation With Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to describe the "fat brook" (FB) in the popliteal fossa of a cadaver and to evaluate its clinical significance. METHODS: Ten fresh cadaveric knees underwent magnetic resonance imaging and histologic analyses. In addition, magnetic resonance imaging images from 321 patients (108 men, 213 women; mean age, 49.8 years; age range, 5-92 years) were retrospectively reviewed. Two radiologists independently determined the presence/absence of the FB and internal derangement of the knee. RESULTS: The FB was present in all cadaveric specimens without synovial lining or joint communication. In the clinical study, the prevalence of FB was 97.8% (314/321). The FB was associated with effusion (P = 0.001) and tear of the medial meniscus (P = 0.022). There was no significant association between prevalence of FB and age or other structures. Determining FB and internal derangement of the knee had excellent interobserver agreement (concordance correlation coefficient = 0.966, 0.834-1.000). CONCLUSIONS: The FB might be a part of the superficial layer of superficial fascia and not be mistaken for a fat fracture or Morel-Lavallée lesion.

Variations in sural nerve formation pattern and distribution on the dorsum of the foot.

The sural nerve, a cutaneous nerve, is clinically important because it is frequently for nerve conduction testing, biopsy, and harvesting for nerve grafts. This nerve exhibits a wide variety of variation in formation, distribution on the dorsum of the foot, and so on, depending on the population observed. In this study, we examined the variation in the sural nerve in 110 Korean cadavers. Of these cadavers, 86.1% of the sural nerves corresponded to type A, where tibial and peroneal components were united to form the sural nerve. These two components most frequently united (65.9%) in the third quarter of the calf, and when the union position was expressed as a ratio to calf length, it corresponded to 0.408 in men and 0.346 in women, with a statistically significant difference. Due to this sexual dimorphism in addition to shorter calf length in females, the length of the sural nerve was shorter in females (male average length: 14.5 ± 4.8 cm; female average length: 11.4 ± 2.9 cm). In terms of distribution of the lateral dorsal cutaneous nerve, the distal continuation of the sural nerve on the dorsum of the foot, it showed variation in association with the superficial peroneal nerve. The innervation of the sural nerve extended most frequently up to the lateral two and a half toes, solely or in conjunction with the superficial peroneal nerve. Obtaining further information regarding sural nerve variation will be useful for various clinical procedures and interpretation of sural nerve conduction results. Clin. Anat. 30:525-532, 2017. © 2017 Wiley Periodicals, Inc.

Foxp3+ regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow.

Foxp3(+) Treg cells are crucial for maintaining T-cell homeostasis, but their role in B-cell homeostasis remains unclear. Here, we found that Foxp3 mutant scurfy mice had fewer B-lineage cells and progenitors, including common lymphoid progenitors and lymphoid-primed multipotent progenitors, but higher myeloid-lineage cell numbers in BM compared with WT littermates. Homeostasis within the HSC compartment was also compromised with apparent expansion of long- and short-term HSCs. This abnormality was due to the lack of Treg cells, but not to the Treg-cell extrinsic functions of Foxp3 or cell-autonomous defects. Among cytokines enriched in the BM of scurfy mice, IFN-γ affected only B lymphopoiesis, but GM-CSF, TNF, and IL-6 collectively promoted granulopoiesis at the expense of B lymphopoiesis. Neutralization of these three cytokines reversed the hematopoietic defects on early B-cell progenitors in scurfy mice. Treg cells ensured B lymphopoiesis by reducing the production of these cytokines by effector T cells, but not by directly affecting B lymphopoiesis. These results suggest that Treg cells occupy an important niche in the BM to protect B-lineage progenitor cells from excessive exposure to a lymphopoiesis-regulating milieu.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

BACKGROUND: The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. METHODS: This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/µL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). RESULTS: Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. CONCLUSIONS: The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

The medial synovial fold of the posterior cruciate ligament: cadaveric investigation together with magnetic resonance imaging and histology.

OBJECTIVE: The purposes of our study were to analyze magnetic resonance imaging (MRI) and cadaveric findings concerning the medial synovial fold of the posterior cruciate ligament (PCL) and to classify the types of fold according to anatomic location. METHODS: Two musculoskeletal radiologists reviewed MR images of 17 cadaveric knees to classify the types of medial fold of the PCL by consensus. The MRI types were divided into 3 groups. In type A, there was no definitive medial fold; and in type B, inferior-short type, there was a small protrusion of the medial border. Type C, inferior-long type, had a long enough fold to exceed the imaginary line, which is connecting between the medial tibial condyle and posterolateral aspect of the medial femoral condyle. Correlations were sought between the findings derived from the MRI studies and cadaveric dissections. Histologic analyses of the medial fold were also performed. RESULTS: On MRI, the most common type of medial fold was type B (76.4%), followed by type C (11.8%) and type A (11.8%). In the cadaveric investigation, the medial folds of both types B and C were found to project into the medial femorotibial joint. Moreover, there was also a protruding medial fold at the superior aspect of the PCL in the A. Histologic examination of the medial folds revealed collagenous tissue surrounded by synovial cells. CONCLUSIONS: Medial folds of the PCL are normal synovial structures that can be seen by MRI and in cadaveric studies in a large proportion of the population.

Foxp3+ regulatory T cells control humoral autoimmunity by suppressing the development of long-lived plasma cells.

Foxp3(+) regulatory T cells (Tregs) are crucial for maintaining T cell tolerance, but their role in humoral autoimmunity remains unclear. To address this, we combined a model of autoantibody-dependent arthritis (K/BxN) with Foxp3 mutant scurfy mice to generate Treg-deficient K/BxN mice, referred to as K/BxNsf mice. The disease symptoms of K/BxNsf mice were exacerbated, and this coincided with increases in extrafollicular Th cells, follicular Th cells, and germinal centers. Surprisingly, the K/BxNsf mice exhibited an abnormal accumulation of mature plasma cells in their spleens and a corresponding loss of bone marrow plasma cells. The plasma cells were unresponsive to the bone marrow homing chemokine CXCL12, despite normal expression of the chemokine receptor CXCR4. Importantly, they were long-lived and less susceptible to the cytotoxic action of cyclophosphamide. They also expressed less FcγRIIb and were less apoptotic in response to autoantigen-autoantibody immune complexes. This suggests that Tregs control plasma cell susceptibility to cell death induced by engagement of FcγRIIb with immune complexes. Direct cytotoxic effects of Tregs also contribute to the death of plasma cells. Thus, our results reveal that Tregs suppress the emergence of long-lived splenic plasma cells by affecting plasma cell-autonomous mechanisms as well as T cell help, thereby avoiding the persistence of humoral autoimmunity.

Morphology of the zygomaticus minor and its relationship with the orbicularis oculi muscle.

The aim of this study was to examine in detail the anatomic variations in the orbicularis oculi muscle (OOc) and relationship of the zygomaticus minor muscle (ZMi) with the OOc, thereby providing an anatomic basis for explaining facial animation and attachment to the periorbital muscle. Sixty-one hemifaces from embalmed Korean adult cadavers (34 males, 27 females; age range, 45-85 years; mean age, 62.6 years) were used in this study. The prevalence of cases in which the ZMi did not run straight from the upper lip, rather running straight to the corner of the levator labii superioris, was 36.1% (22/61), because the origin of ZMi covered the inferior border of the OOc. The prevalence of mixing of the belly of the orbital part of the outer edge of the OOc with the ZMi was 88.5%, and that of blending of the ZMi band into the lower inner corner of the OOc was 55.7%. The area of blending of the OOc and ZMi was located 17.8 mm down from the Frankfort plane and 8.9 mm lateral to the vertical line between the lateral canthus and the Frankfort plane in the lateral part of the OOc. At this position, the mixed belly extends medially for a distance of 16 mm. This research has identified the exact location where the ZMi and OOc blend and determined the relationship between the ZMi and the suborbicularis oculi fat. This result will be given as basic data for understanding facial expressions and for performing composite rhytidectomy.

Compatibility of the HINTEGRA prostheses with Korean ankles as evaluated on the basis of cadaveric measurements.

The purpose of this study was to obtain anatomical measurements of the distal tibia and talus of Korean ankles and to evaluate, based on those measurements, the compatibility of the HINTEGRA prostheses in the context of total ankle replacement (TAR). We measured the length, width, height, and angles of the distal tibia and talus of 51 cadavers and compared these measurements with the corresponding dimensions of the HINTEGRA prostheses. The male ankles were larger than the female ones as was expected, but their overall shapes did not differ, which fact validates use of the prostheses irrespective of patients' sex. The dimensions of the talus itself did not differ significantly from those previously reported for American whites and blacks and South African whites. This might suggest a possibility that the HINTEGRA prostheses, being used in these countries, would be compatible to Korean ankles, too. In fact, the length range of the talar components was generally compatible with those derived from cadaveric measurements of the trochlea. However, the widths of the tibial and talar components were not completely compatible to Korean ankles. Above all, the length of the large-sized tibial components was much longer than the largest ankles, which would confine the choice of prosthesis mainly to small-sized ones for arthroplasty in Korea. Even though these prostheses are currently used, some modifications are needed to extend their usability in Korea, such as shortening and width/length ratio adjustment of the tibial component, and of the talar component accordingly.

A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.

Rheumatoid arthritis is a joint-specific autoimmune inflammatory disease of unknown etiology. The K/BxN mouse is a model of rheumatoid arthritis that is thought to be mainly due to autoantibody-mediated inflammatory responses. We showed previously that homeostatic proliferation of autoreactive CD4(+) T cells is required for disease initiation in the K/BxN mice. In this study, we show that the homeostatically proliferating CD4(+)CD25(-) T cells produce IL-21. We generated IL-21R-deficient (IL-21R(-/-)) K/BxN mice and found that these mice were completely refractory to the development of spontaneous arthritis. They contained fewer CD4(+) T cells with a reduced proportion of homeostatically proliferating cells, fewer follicular Th cells, and, surprisingly, more Th17 cells than their control counterparts. They also failed to develop IgG1(+) memory B cells and autoantigen-specific IgG1 Ab-secreting cells. IL-21 induced expression of receptor activator of NF-kappaB ligand (RANKL) a regulator of osteoclastogenesis, and few RANKL-expressing infiltrates were found in the synovia of IL-21R(-/-) K/BxN mice. Thus, our results demonstrate that IL-21 forms a positive feedback autocrine loop involving homeostatically activated CD4(+) cells and that it plays an essential role in the development of autoimmune arthritis by mechanisms dependent on follicular Th cell development, autoreactive B cell maturation, and RANKL induction but independent of Th17 cell function. Consistent with this, in vivo administration of soluble the IL-21R-Fc fusion protein delayed the onset and progression of arthritis. Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis.

Left costomediastinal recess of the pleura, the potential pleural space anterior to the heart.

OBJECTIVE: To investigate clinical implications of the left costomediastinal recess of the pleura. METHODS: The left anterior pleural anatomy was studied in 12 cadavers. Chest computed tomography (CT) scans of 68 healthy/near-healthy patients were reviewed for the recess. Twenty pleural lesions in the recess were analyzed on CT. Eight cases of left paracardiac pericardiocentesis were analyzed for pleural complications. RESULTS: Two fresh cadavers showed the recess to be wider downward, measuring 75 and 55 mm in width at the sixth intercostal space. None of the 68 healthy/near- healthy CT scans displayed the recess. Twenty recess lesions were connected to similar pleural lesions surrounding the left lung (n = 19) or showed an isolated lesion therein only partly facing the left lung (n = 1). Ipsilateral pleural effusion complicated 3 of 7, successful left paracardiac pericardiocentesis. CONCLUSION: Regardless of their contiguity with the lung, the differential diagnosis of precordial lesions should include pleural diseases in the recess. Left anterior pericardiocentesis unavoidably violates the intervening recess, sometimes causing pleural effusion.

Variations in the trabecular bone ratio of the maxilla according to sex, age, and region using micro-computed tomography in Koreans.

These cortical and trabecular bones maintain general bone structure. Bone mineral density (BMD) changes according to increasing age, sex, and teeth loss. From previous studies, the evaluation of BMD changes depended on conventional radiographic analysis. This study investigated the trabecular bone ratio (TBR) in maxillary bone samples based on data obtained by micro-computed tomography and estimated variations in BMD according to age, sex, and tooth loss. Thirty-eight specimens were scanned with micro-computed tomography and reconstructed three-dimensionally. Sections were made parallel to the axis of each tooth, and the TBR was measured. Data were statistically analyzed with 1-way analysis of variance and paired t-tests (α=0.05). The TBR differed significantly (P<0.05) in each tooth region in the dentate group but not in the edentulous group. The mean TBR was higher in men than in women. The TBR reduced more with increasing age in the dentate group than in the edentulous group. The TBR varies according to the presence of teeth, sex, and age in specific teeth regions.

Bacillus subtilis-specific poly-gamma-glutamic acid regulates development pathways of naive CD4(+) T cells through antigen-presenting cell-dependent and -independent mechanisms.

Peripheral naive CD4(+) T cells selectively differentiate to type 1 T(h), type 2 T(h) and IL-17-producing T(h) (T(h)17) cells, depending on the priming conditions. Since these subsets develop antagonistically to each other to elicit subset-specific adaptive immune responses, balance between these subsets can regulate the susceptibility to diverse immune diseases. The present study was undertaken to determine whether poly-gamma-glutamic acid (gamma-PGA), an edible and safe exopolymer that is generated by microorganisms such as Bacillus subtilis, could modulate the development pathways of T(h) subsets. The presence of gamma-PGA during priming promoted the development of T(h)1 and T(h)17 cells but inhibited development of T(h)2 cells. gamma-PGA up-regulated the expression of T-bet and ROR-gammat, the master genes of T(h)1 and T(h)17 cells, respectively, whereas down-regulating the level of GATA-3, the master gene of T(h)2 cells. gamma-PGA induced the expression of IL-12p40, CD80 and CD86 in dendritic cells (DC) and macrophages in a Toll-like receptor-4-dependent manner, and the effect of gamma-PGA on T(h)1/T(h)2 development was dependent on the presence of antigen-presenting cells (APC). Furthermore, gamma-PGA-stimulated DC favored the polarization of naive CD4(+) T cells toward T(h)1 cells rather than T(h)2 cells. In contrast, gamma-PGA affected T(h)17 cell development, regardless of the presence or absence of APC. Thus, these data demonstrate that gamma-PGA has the potential to regulate the development pathways of naive CD4(+) T cells through APC-dependent and -independent mechanisms and to be applicable to treating T(h)2-dominated diseases.

Trabecular bone ratio of mandible using micro-computed tomography in Korean.

Cortical bone and trabecular portion play important roles in maintaining the general structure of bone. It has been reported that a decrease in bone mineral density is related with increasing age, sex, and teeth loss. However, most of the studies were done with conventional radiographic analysis. In addition, data from Korean population are rare. The aim of this study was to analyze trabecular pattern of the mandible using micro-computed tomography. Thirty-nine specimens of the mandible were prepared. Specimens were scanned with micro-computed tomography and reconstructed three-dimensionally. Sections were made parallel to the axis of each tooth. Trabecular bone ratio (TBR) was measured. Data were statistically analyzed with 1-way analysis of variance (alpha = 0.05). There was a statistically significant difference of TBR between dentate and edentulous mandibles in the molar region. Trabecular bone ratio of edentulous mandible in males was greater than that in females. Trabecular bone ratio of dentate mandibles reduced regularly with increasing age, whereas that of edentulous mandibles did not. It could be concluded that there were statistically significant differences in TBR according to presence of tooth, sex, and increasing age on specific areas.

Effects of maternal hyperthermia on myogenesis-related factors in developing upper limb.

BACKGROUND: Maternal hyperthermia is one causative factor in various congenital anomalies in experimental animals and humans. In the present study, we assessed the effects of high temperature on limb myogenesis in mice. METHODS: Pregnant mice, C57BL/6 strain, were exposed to hyperthermia (43 degrees C, 5 minutes) on embryonic day (ED) 8. Fetuses on ED 11, 13, 15, and 17 and neonates on postnatal day (PD) 1 were collected. To characterize the effects of hyperthermia on myogenesis-related factors Pax3, MyoD, myogenin, and myosin heavy chain (MyHC) during skeletal muscle development, we performed RT-PCR, western blotting, immunohistochemistry, and transmission electron microscopy. RESULTS: Pax3 gene expression was still detected on ED 13 in hyperthermia-exposed fetuses. The expression of MyoD protein was down-regulated in fetuses exposed to hyperthermia. In contrast, myogenin and MyHC protein expression were up-regulated on PD 1 and ED 17, respectively, in the group exposed to hyperthermia. Immunohistochemical analysis confirmed the findings from western blot analysis. Compared with control neonates, a TEM study revealed immature muscle fibers in PD 1 hyperthermia neonates. Thus, our studies showed that maternal hyperthermia induced delayed expression of Pax3 and inhibited expression of MyoD proteins, which are known to play important roles in migration of myogenic progenitor cells, and in myoblast proliferation. In addition, maternal hyperthermia also delayed the expression of myogenin protein for the formation of myotubes, and MyHC protein, which is one of the final muscle differentiation factors. CONCLUSION: Our data suggest that maternal hyperthermia delays limb myogenesis in part by disregulating the expression of key myogenesis-related factors.

Position and size of the sphenoid door jamb in the lateral orbital wall for the orbital decompression.

The aim of this study was to identify the three-dimensional topography of the sphenoid door jamb (SDJ) in the lateral orbital wall and to propose navigational guidelines for safe deep lateral decompression using surgical landmarks. The 120 orbits and SDJs of 60 subjects were three-dimensionally reconstructed using Mimics software. The mean volumes of the orbit and SDJ were 24.3 mm3 and 2.0 mm3, respectively. The mean distances from the lateral orbital margin (LOM) to the anterior and posterior margins of the SDJ were 13.2 and 36.3 mm, respectively. The mean distances from the superior orbital fissure to the LOM and to the posterior margin of the SDJ were 40.2 mm and 4.6 mm, respectively. The mean distances from the inferior orbital fissure (IOF) to the anterior and posterior margins of the SDJ were 3.8 mm and 20.5 mm, respectively. In the superior approach of the orbit, it can be predicted that the area up to 3 cm posterior from the LOM is safe, while 1 cm posterior from the safe zone could be a dangerous zone. In the inferior approach of the orbit, the safe area will be about 1 cm posterior from the anterior tip of the IOF, and the area up to 1 cm posterior from the safe zone should be approached with extreme care.

CD4+CD25+ regulatory T cells selectively diminish systemic autoreactivity in arthritic K/BxN mice.

Although the arthritis symptoms observed in the K/BxN model have been shown to be dependent on the functions of T and B cells specific to the self antigen glucose-6-phosphate isomerase, less is known about the in vivo roles of CD4(+)CD25(+) regulatory T (T(reg)) cells in the pathology of K/BxN mice. We determined the quantitative and functional characteristics of the T(reg) cells in K/BxN mice. These mice contained a higher percentage of Foxp3(+) T(reg) cells among the CD4(+) T cells than their BxN littermates. These T(reg) cells were anergic and efficiently suppressed the proliferation of naïve CD4(+) T cells and cytokine production by effector CD4(+) T cells in vitro. Antibody-mediated depletion of CD25(+) cells caused K/BxN mice to develop multi-organ inflammation and autoantibody production, while the symptoms of arthritis were not affected. These results demonstrate that despite the inability of the T(reg) cells to suppress arthritis development, they play a critical role protecting the arthritic mice from systemic expansion of autoimmunity.

Functions of metallothionein generating interleukin-10-producing regulatory CD4+ T cells potentiate suppression of collagen-induced arthritis.

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. Naïve CD4+ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, TGF-gamma, and repressor of GATA, but more IFN-gamma and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove naïve wild-type CD4+ T cells to differentiate into cells producing more IL-10 and TGF-beta, but less IFN-gamma than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10- and TGF-beta-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

Erratum: Agrobacterium sp.-derived ß-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study.

[This corrects the article on p. 43 in vol. 11, PMID: 28194264.].

Agrobacterium sp.-derived ß-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study.

BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ß-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of 4,000-8,000 cells/µL were participated and randomly assigned to take two capsules per day containing either 350 mg ß-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ß-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ß-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ß-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ß-1,3-glucan did not significantly modulate the levels of IFN-γ, IL-2, IL-4, IL-6, IL-12, TNF-α and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ß-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ß-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.