Jae-Hoon Choi

Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract

Lung DCs induce the expression of gut-homing molecules on T cells, resulting in their migration to the GI tract and protection against Salmonella infection after immunization

Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells

Plasmacytoid dendritic cells (pDCs) are unique bone-marrow-derived cells that produce large amounts of type I interferon in response to microbial stimulation. Furthermore, pDCs also promote Txa0cell tolerance in sterile-inflammation conditions. However, the immunomodulatory role of aortic pDCs in atherosclerosis has been poorly understood. Here, we identified functional mouse and human pDCs in the aortic intima and showed that selective, inducible pDC depletion in mice exacerbates atherosclerosis. Aortic pDCs expressed CCR9 and indoleamine 2,3-dioxygenase 1 (IDO-1), an enzyme involved in driving the generation of regulatory Txa0cells (Tregs). As a consequence, loss of pDCs resulted in decreased numbers of Tregs and reduced IL-10 levels in the aorta. Moreover, antigen presentation by pDCs expanded antigen-specific Tregs in the atherosclerotic aorta. Notably, Tregs ablation affected pDC homeostasis in diseased aorta. Accordingly, pDCs in human atherosclerotic aortas colocalized with Tregs. Collectively, we identified a mechanism of atheroprotection mediated by tolerogenic aortic pDCs.

CD137-inducing factors from T cells and macrophages accelerate the destabilization of atherosclerotic plaques in hyperlipidemic mice

CD137 (4‐1BB), a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed in atherosclerotic plaques, and to promote lesion formation. However, the role of CD137 in mediating atherosclerotic plaque stability and the possible underlying molecular and cellular mechanisms are poorly understood. Here, apolipoprotein E‐deficient (ApoE‐/‐) and CD137‐deficient ApoE‐/‐(ApoE‐/‐ CD137‐/‐) mice fed a chow diet for 66 wk were used. CD137 induces plaque instability, which is characterized by increased plaque necrosis, decreased collagen content, decreased vascular smooth muscle cell (VSMC) content, and increased macrophage infiltration. CD137 also increases the infiltration of effector T (Teff) cells into plaque lesion sites, resulting in increased interferon‐γ (IFN‐γ) expression. Interestingly, Teff‐cell‐derived IFN‐γ inhibits collagen synthesis in atherosclerotic plaques. Furthermore, CD137 activation increases the apoptosis of VSMCs, possibly by decreasing the antiapoptotic regulator, Bcl‐2, and subsequently up‐regulating cleaved caspase‐3. In macrophages, activation of CD137 signaling boosted the oxidized low density lipoprotein‐induced expression of matrix metalloproteinase 9 via the p38 mitogen‐activated protein kinase and extracellular signal‐regulated kinase1/2 signaling pathways. In summary, activation of CD137 signaling decreases the stability of advanced atherosclerotic plaques via its combined effects on Teff cells, VSMCs, and macrophages.—Jung, I.‐H., Choi, J.‐H., Jin, J., Jeong, S.‐J., Jeon, S., Lim, C., Lee, M.‐R., Yoo, J.‐Y., Sonn, S.‐K., Kim, Y. H., Choi, B. K., Kwon, B. S., Seoh, J.‐Y., Lee, C. W., Kim, D.‐Y., Oh, G. T. CD137‐inducing factors from T cells and macrophages accelerate the destabilization of atherosclerotic plaques in hyperlipidemic mice. FASEB J. 28, 4779–4791 (2014). www.fasebj.org

Complete septal extension grafts using porous high-density polyethylene sheets for the westernization of the Asian nose.

Background: In Asian rhinoplasty, most patients need correction of the nasal tip and columella along with dorsal augmentation. A complete septal extension graft can effectively and concomitantly correct less projected tips, retracted columellar bases, and acute columella-labial angles. However, the amount of septal cartilage is not sufficient as a source for the graft; therefore, the authors used porous high-density polyethylene sheets as their graft material. Methods: Fifty-eight patients were enrolled in the study between April of 1994 and July of 2001. The authors evaluated a total of 11 measurement items (three for nasal tip, three for columella, two for alar shape or flaring, one for nostril shape, and two for symmetry of the alae and columella) by photogrammetry using standardized clinical photogrammetric techniques. Results: Nasal tip projection, nasal bridge length, height of nose, and columella-labial angle increased significantly during an average follow-up period of 21 months, but nostril axis inclination, columellar length (Rt-Lt), and alar length (Rt-Lt) decreased significantly during the same study period. Implant exposure was noted in two cases, which was resolved by trimming the implants. Minor complications were stiffness of the columella (12 patients), buckling of the implant (nine patients), and excessive columellar show (two patients). Conclusions: A complete septal extension graft resulted in a more projected and caudally lengthened nasal tip; in addition, retracted columella and the acute columella-labial angle were improved aesthetically. Most complications were lower risk and preventable. Therefore, with careful use of porous high-density polyethylene, the authors could modify Asian noses into more Westernized noses. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Comparison of endoscopic endonasal reduction and transcaruncular reduction for the treatment of medial orbital wall fractures.

Currently, endoscopic endonasal reduction and transcaruncular reduction are frequently used as surgical treatments for medial orbital wall fractures. However, these 2 surgical techniques have not been comprehensively compared using objective criteria. Therefore, the results of these 2 techniques were compared retrospectively using 8 objective criteria in patients with medial orbital wall fracture. This study included 48 medial orbital wall fracture patients treated from June 1993 to July 2006: 29 had endoscopic endonasal reduction and 19 had transcaruncular reduction. Computed tomographic scans, double vision field testing for diplopia using Goldmann perimetry, and Hertel exophthalmometer (Richmond Products, Albuquerque, NM) were done pre- and postsurgery. The average follow-up period was 70.8 months. Among patients with pure medial orbital wall fractures, the average reduction rate was 89.2% for the endoscopic endonasal reduction group and 90.7% for the transcaruncular reduction group. One case in the endoscopic endonasal reduction group had a more than 2-mm enophthalmos after surgery. The diplopia correction rate was 1.8% in the endoscopic endonasal reduction group and 2.7% in the transcaruncular reduction group. None of the above differences was statistically significant. However, among patients with pure medial orbital wall fractures compared with the transcaruncular reduction group, the average operation time, the average hospital stay, and the average cost were significantly greater in the endoscopic endonasal reduction group. The 2 surgical methods had a similar effectiveness; however, transcaruncular reduction seemed to be more advantageous with respect to the operation time, the length of hospital stay, and cost.

Involvement of Immune Cell Network in Aortic Valve Stenosis: Communication between Valvular Interstitial Cells and Immune Cells

Aortic valve stenosis is a heart disease prevalent in the elderly characterized by valvular calcification, fibrosis, and inflammation, but its exact pathogenesis remains unclear. Previously, aortic valve stenosis was thought to be caused by chronic passive and degenerative changes associated with aging. However, recent studies have demonstrated that atherosclerotic processes and inflammation can induce valvular calcification and bone deposition, leading to valvular stenosis. In particular, the most abundant cell type in cardiac valves, valvular interstitial cells, can differentiate into myofibroblasts and osteoblast-like cells, leading to valvular calcification and stenosis. Differentiation of valvular interstitial cells can be trigged by inflammatory stimuli from several immune cell types, including macrophages, dendritic cells, T cells, B cells, and mast cells. This review indicates that crosstalk between immune cells and valvular interstitial cells plays an important role in the development of aortic valve stenosis.

High cholesterol diet induces IL-1β expression in adult but not larval zebrafish.

Recently, it has been demonstrated that high cholesterol diet induced hypercholesterolemia and vascular lipid oxidation and accumulation in zebrafish larvae, suggesting that zebrafish is a new promising atherosclerosis model in addition to mouse models. However, up to date, there was no report regarding inflammatory cytokine expression during the lipid accumulation in zebrafish larva and adult fish. In this study, we first demonstrated the expression levels of IL-1β and TNF-α in high cholesterol diet (HCD)-fed zebrafish larvae, and found that although HCD induced vascular lipid accumulation, the cytokine expressions in the larvae were not changed by HCD. Furthermore, there was no significant difference in leukocyte accumulation in vessels between control and HCD fed group. But prolonged HCD induced IL-1β expression in spleen and liver compared to those of control zebrafish, and produced very early stage of fatty streak lesion in dorsal aorta of 19 week HCD-fed zebrafish. These results indicate that HCD induced hypercholesterolemia and atherosclerotic changes in zebrafish are very early stage, and suggest the necessity of the generation of mutant zebrafish having a disruption in a lipid metabolism-related gene leading to severe hypercholesterolemia and advanced atherosclerosis.

Reconstruction of defects after excision of facial skin cancer using a venous free flap.

After extensive excision of skin cancer on the face, or when skin cancer is located on the 3-dimensional structures of the face, reconstruction with a local flap can be impossible, or clinicians are reluctant to reconstruct defects with a skin graft because of postoperative contraction, hyperpigmentation, or other complication. Instead, an arterialized venous free flap can be used as an alternative method of reconstruction to prevent distortion and recurrence. Eight patients underwent surgery with an arterialized venous-free flap. We evaluated the cosmetic results using ordinary scale methods on the basis of 4 categories (color, contour, texture, and distortion of surrounding structures) and recurrence and metastases of skin cancer physically. The follow-up period ranged between 24 and 48 months, with an average of 33 months. All of the soft-tissue defects made by excising the tumor were reconstructed with good outcomes, except for 1 case. Regarding the cosmetic evaluation, the color was fair, the contour and texture were good, absence of distortion of surrounding structures was excellent, and the overall results in most all cases were good. There were no recurrences or metastases during the follow-up period. The arterialized venous free flap is an alternative plan among several reconstruction methods when skin cancer on the face is extensively excised.

Prdx1 (peroxiredoxin 1) deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux

ABSTRACT Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous antioxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the antioxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other antioxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages. Prdx1-deficient macrophages had higher intracellular cholesterol mass and lower cholesterol efflux compared with wild type. This perturbation in cholesterol homeostasis was due to impaired lipophagic cholesterol hydrolysis caused by excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity. Notably, impairment of both lipophagic flux and cholesterol efflux was restored by the 2-Cys PRDX-mimics ebselen and gliotoxin. Consistent with this observation, apoe −/− mice transplanted with bone marrow from prdx1−/−apoe−/− mice had increased plaque formation compared with apoe−/− BM-transplanted recipients. This study reveals that PRDX1 is crucial to regulating lipophagic flux and maintaining macrophage cholesterol homeostasis against oxidative stress. We suggest that PRDX1-dependent control of oxidative stress may provide a strategy for treating atherosclerosis and autophagy-related human diseases.

Local Immune Responses in Children and Adults with Allergic and Nonallergic Rhinitis

Background Allergic rhinitis (AR) is the most common allergic disease but little is known about the difference of local immune responses in children and adults with AR. Objective To compare local immune responses between children and adults with AR and nonallergic rhinitis (NAR), and to investigate whether the association of local and systemic immune responses is different between the two age groups. Methods Fifty-one patients with chronic rhinitis were enrolled and grouped into children (N = 27, mean age 7.2 years) and adults (N = 24, mean age 29.9 years). Diagnosis of AR was based on symptoms, skin prick tests and serum specific IgEs. Nasal lavage (NAL) fluids were collected from all subjects and used to measure the levels of total IgE, specific IgEs to house dust mites (Dp and Df), and cytokines (TNF-α, IL-4, IL-10, IL-17A and IFN-γ). Flow cytometry was used to measure inflammatory cell types in NAL fluids. Results AR had significantly increased local levels of total IgE and specific IgEs to Dp and Df compared with NAR in both age groups (P < 0.05). Nasal eosinophils % (P = 0.01) was significantly increased only in children with AR. Local-systemic correlations of total IgE (r = 0.662, P = 0.000) and eosinophil % (r = 0.461, P = 0.015) between the peripheral blood and NAL fluids were found only in children. Moreover, children had correlations between total IgE and eosinophil % in the peripheral blood (r = 0.629, P = 0.001) and in NAL fluids (r = 0.373, P = 0.061). Conclusion Elevated local IgE is a common feature of AR in children and adults. Local measures in NAR showed naïve state of immune response which disagree with the hypothesis of local allergic rhinitis. Children showed intense local inflammation and close local-systemic interactions compared to adults supporting pediatric AR as a distinct feature.