Innate immune systems

Innate immune systems

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The study of ILC2 in allergy and immune diseases

ILC2 (originally named “natural helper cells”), found in fat associated lymphoid clusters (FALC), do not express antigen-specific receptors found on many other immune cells. Nevertheless, they respond rapidly to the IL-25 and IL-33 secreted by damaged epithelial cells by secreting large amounts of IL-5 and IL-13, which leads to parasite elimination and induction of allergic responses .

Figure 1

The mechanism for activation of ILC2 differs from that of T helper 2 (Th2) cells, which also produce type 2 cytokines: Th2 cells do so in an antigen-specific manner, whereas ILC2 do not.

The discovery of ILC2 confirmed the existence of the ILC family, which comprises lymphocytes with helper activity in the innate system. There are now three categories of ILCs. ILC1 produce IFNγ and have antiviral and antitumor immunity. As mentioned above, ILC2 produce IL-5 and IL-13 and are associated with parasitic responses and allergies. Finally, ILC3 secrete IL-17 and IL-22 and are associated with autoimmune diseases.

Accordingly, the ILC family as a whole differ from Th cells in a number of ways. Th cells take several days to differentiate, while ILCs are present in normal tissues as mature lymphocytes. Thus, besides their role in immune responses, ILCs are believed to contribute to tissue homeostasis. ILC2, in particular, are found in tissues throughout the body including the lungs, bone, brain, muscle, skin and others. In addition to allergic reactions, they are associated with chronic inflammation in obesity and fibrosis, and play a role in rheumatoid arthritis, an autoimmune disease. Furthermore, they have been reported to interact with non-immune cells, promote the proliferation of tissue stem cells and epithelial cells for regeneration, and localize around nerves to regulate neurotransmitters.

Much of the above research has focused on mouse models, and many efforts are underway to confirm that the same properties hold true in humans. Genetic polymorphism studies have suggested ILC2-related genes such as IL-33 are associated with disease and ILC2 is being investigated as a new clinical target .

Figure 2

With all the above points in mind, our laboratory is conducting comprehensive analysis of ILC2, including investigation of the mechanisms for differentiation, signaling and activation and also partner cell types. The expectation is that this research will lead to new models and therapies for related immune diseases such as allergies, fibrosis, and metabolic diseases.

Principal Investigator

Kazuyo Moro Professor

Research field:Innate immune systems
+81-6-6879-3820
moroilc.med-osaka-u.ac.jp
Education History
2003 DDS, Nihon University, Japan
2010 PhD, Keio University, Japan
Research and career history
2003 Research Assistant, COE, Keio University School of Medicine, Japan
2007 Assistant Professor, Keio University School of Medicine, Japan
2008 Assistant Professor, Global COE, Keio University School of Medicine, Japan
2011 Research Fellow, PRESTO, JST, Japan
2011 Assistant Professor, Immunology, Keio University School of Medicine, Japan
2012 Sub Team Leader, RIKEN RCAI, Yokohama, Japan
2013 Senior Research Fellow, RIKEN IMS, Yokohama, Japan
2013 Guest Associate Professor, Yokohama City University, Japan
2015 Team Leader, Innate Immune System, RIKEN IMS, Yokohama, Japan
2016 Guest Professor, Yokohama City University, Japan
2016 Program Officer, AMED, Research Project for Intractable diseases, Japan
2019 Professor, Osaka University Graduate School of Medicine, Japan
 

Publication

Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S; Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 463 (7280)540-544 (2010)
Furusawa J, Moro K, Motomura Y, Okamoto K, Zhu J, Takayanagi H, Kubo M, Koyasu S; Critical role of p38 and GATA3 in natural helper cell function. Journal of immunology. 191 (4)1818-1826 (2013)
Kabata H, Moro K (equal contribution), Fukunaga K, Suzuki Y, Miyata J, Masaki K, Betsuyaku T, Koyasu S, Asano K; Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun. 42675 (2013)
Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, Fagarasan S, Mielke LA, Afshar-Sterle S, Masters SL, Nakae S, Saito H, Wentworth JM, Li P, Liao W, Leonard WJ, Smyth GK, Shi W, Nutt SL, Koyasu S, Kallies A; The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol. 16 (3)276-285 (2015)
Moro K, Ealey KN, Kabata H, Koyasu S; Isolation and analysis of group 2 innate lymphoid cells in mice. Nature protocols. 10 (5)792-806 (2015)
Moro K, Koyasu S; Innate lymphoid cells, possible interaction with microbiota. Seminars in immunopathology. 37 (1)27-37 (2015)
Moro K, Kabata H, Tanabe M, Koga S, Takeno N, Mochizuki M, Fukunaga K, Asano K, Betsuyaku T, Koyasu S; Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses. Nat Immunol. 17 (1)76-86 (2016)
Ealey KN, Moro K, Koyasu S; Are ILC2s Jekyll and Hyde in airway inflammation? Immunological reviews. 278 (1)207-218 (2017)
Koga S, Hozumi K, Hirano KI, Yazawa M, Terooatea T, Minoda A, Nagasawa T, Koyasu S, Moro K; Peripheral PDGFRalpha(+)gp38(+) mesenchymal cells support the differentiation of fetal liver-derived ILC2. J Exp Med. 215 (6)1609-1626 (2018)
Kabata H, Moro K, Koyasu S; The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms. Immunological reviews. 286 (1)37-52 (2018)

Prize

2011 27th Inoue Research Award for Young Scientists
2016 11th Japanese Society of Immunology (JSI) Young Investigator Award
2017 13th Japan Society for the Promotion of Science (JSPS) Prize
2017 13th Japan Academy Medal
2018 8th Nagase Award