Indoleamine 2,3-Dioxygenase Is Not a Pivotal Regulator Responsible for Suppressing Allergic Airway Inflammation through Adipose-Derived Stem Cells.
BACKGROUND
Although indoleamine 2,3-dioxygenase (IDO)-mediated immune suppression of mesenchymal stem cells (MSCs) has been revealed in septic and tumor microenvironments, the role of IDO in suppressing allergic airway inflammation by MSCs is not well documented. We evaluated the effects of adipose-derived stem cells (ASCs) on allergic inflammation in IDO-knockout (KO) asthmatic mice or asthmatic mice treated with ASCs derived from IDO-KO mice.


RESULTS
ASCs were injected intravenously in wild-type (WT) and IDO-KO asthmatic mice. Furthermore, asthmatic mice were injected with ASCs derived from IDO-KO mice. We investigated the immunomodulatory effects of ASCs between WT and IDO-KO mice or IDO-KO ASCs in asthmatic mice. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet hyperplasia, and serum concentrations of total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and enhanced Th1 cytokine (interferon-γ) and regulatory cytokines (IL-10, TGF-β) in BALF and lung draining lymph nodes (LLNs). ASCs led to significant increases in regulatory T-cells (Tregs) and IL-10+ T cell populations in LLNs. However, the immunosuppressive effects of ASCs did not significantly differ between WT and IDO-KO mice. Moreover, ASCs derived from IDO-KO mice showed immunosuppressive effects in allergic airway inflammation.


CONCLUSIONS
IDO did not play a pivotal role in the suppression of allergic airway inflammation through ASCs, suggesting that it is not the major regulator responsible for suppressing allergic airway inflammation.
Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Kyu-Sup
KS
Cho
Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Mi-Kyung
MK
Park
Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
Sue-Jean
SJ
Mun
Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Hee-Young
HY
Park
Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Hak-Sun
HS
Yu
Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
Hwan-Jung
HJ
Roh
D000273:Adipose Tissue / Q000166:cytology* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D007249:Inflammation / Q000628:therapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D018655:Lymphocyte Count; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D016210:Methacholine Chloride / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018793:Interleukin-13; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D016210:Methacholine Chloride; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma