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Woo, Yeon Duk,Koh, Jaemoon,Kang, Hye-Ryun,Kim, Hye Young,Chung, Doo Hyun Elsevier 2018 The journal of allergy and clinical immunology Vol.142 No.6
<P><B>Background</B></P> <P>The chemokine X-C motif chemokine ligand 1 (XCL1)–X-C motif chemokine receptor 1 (XCR1) axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in patients with allergic asthma.</P> <P><B>Objective</B></P> <P>In the present study we explored whether the invariant natural killer T (<I>i</I>NKT) cell–mediated XCL1-XCR1 axis regulated allergic asthma.</P> <P><B>Methods</B></P> <P>Ovalbumin (OVA)– or house dust mite–induced asthma was developed in XCL1 or XCR1 knockout (KO) mice.</P> <P><B>Results</B></P> <P>XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103<SUP>+</SUP> dendritic cells (DCs), and T<SUB>H</SUB>2 responses in the lungs compared with wild-type (WT) mice during OVA- or house dust mite–induced asthma. These effects were reversed by intratracheal administration of recombinant XCL1 or adoptive transfer of CD103<SUP>+</SUP> DCs but not CD11b<SUP>+</SUP> DCs into XCL1 KO mice. Moreover, <I>i</I>NKT cells highly expressed XCL1 both <I>in vitro</I> and <I>in vivo</I>. On intranasal α-galactosyl ceramide challenge, CD103<SUP>+</SUP> DC numbers in the lungs were increased in WT but not XCL1 KO mice. Furthermore, adoptive transfer of WT <I>i</I>NKT cells increased AHR, CD103<SUP>+</SUP> DC recruitment, and T<SUB>H</SUB>2 responses in the lungs of CD1d KO mice during OVA-induced asthma, whereas adoptive transfer of XCL1-deficient <I>i</I>NKT cells did not. In human patients, percentages and XCL1 production capacity of <I>i</I>NKT cells from PBMCs were greater in patients with asthma than in healthy control subjects.</P> <P><B>Conclusion</B></P> <P>These data demonstrate that the <I>i</I>NKT cell–mediated XCL1-XCR1 axis promotes AHR by recruiting CD103<SUP>+</SUP> DCs into the lung in patients with allergic asthma.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Shin, Jae Woo,Ryu, Seungwon,Ham, Jongho,Jung, Keehoon,Lee, Sangho,Chung, Doo Hyun,Kang, Hye-Ryun,Kim, Hye Young Korean Society for Molecular and Cellular Biology 2021 Molecules and cells Vol.44 No.8
Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. In vitro co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.
Kim, Jihyun,Chang, Yuna,Bae, Boram,Sohn, Kyoung-Hee,Cho, Sang-Heon,Chung, Doo Hyun,Kang, Hye Ryun,Kim, Hye Young Elsevier 2019 The journal of allergy and clinical immunology Vol.143 No.5
<P><B>Background</B></P> <P>Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the participation of other types of ILCs in the development of asthma remains unclear.</P> <P><B>Objective</B></P> <P>This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.</P> <P><B>Methods</B></P> <P>Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs.</P> <P><B>Results</B></P> <P>In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage–related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage–related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage–dominant profile.</P> <P><B>Conclusion</B></P> <P>A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Hae Suk Cheong,Ki-Tae Kwon,Ji-Young Rhee,Seong Yeol Ryu,Dong Sik Jung,Sang Taek Heo,Sang Yop Shin,Doo Ryun Chung,Kyong Ran Peck,Jae-Hoon Song 대한기생충학열대의학회 2009 The Korean Journal of Parasitology Vol.47 No.3
The incidence of imported malaria has been increasing in Korea. We reviewed data retrospectively to evaluate the epidemiology, clinical features, and outcomes of imported malaria from 1995 to 2007 in a university hospital. All patients diagnosed with imported malaria were included. Imported malaria was defined as a positive smear for malaria that was acquired in a foreign country. A total of 49 patients (mean age, 35.7 year; M : F = 38 : 11) were enrolled. The predominant malarial species was Plasmodium falciparum (73.5%), and the most frequent area of acquisition was Africa (55.1%), followed by Southeast Asia (22.4%) and South Asia (18.4%). Fourteen-patients (30.6%) suffered from severe malaria caused by P. falciparum and 1 patient (2.0%) died of multiorgan failure. Most of the patients were treated with mefloquine (79.2%) or quinine (10.2%); other antimalarial agents had to be given in 13.2% treated with mefloquine and 44.4% with quinine due to adverse drug events (ADEs). P. falciparum was the most common cause of imported malaria, with the majority of cases acquired from Africa, and a significant number of patients had severe malaria. Alternative antimalarial agents with lower rates of ADEs might be considered for effective treatment instead of mefloquine and quinine.