Type 2 innate lymphoid cells constitutively express arginase-I in the naive and inflamed lung.
Arg1 is produced by AAMs and is proposed to have a regulatory role during asthma and allergic inflammation. Here, we use an Arg1 reporter mouse to identify additional cellular sources of the enzyme in the lung. We demonstrate that ILC2s express Arg1 at rest and during infection with the migratory helminth Nippostrongylus brasiliensis. In contrast to AAMs, which express Arg1 following IL-4/IL-13-mediated STAT6 activation, ILC2s constitutively express the enzyme in a STAT6-independent manner. Although ILC2s deficient in the IL-33R subunit T1/ST2 maintain Arg1 expression, IL-33 can regulate total lung Arg1 by expanding the ILC2 population and by activating macrophages indirectly via STAT6. Finally, we find that ILC2 Arg1 does not mediate ILC2 accumulation, ILC2 production of IL-5 and IL-13, or collagen production during N. brasiliensis infection. Thus, ILC2s are a novel source of Arg1 in resting tissue and during allergic inflammation.
1.UCSF, 513 Parnassus Ave., S-1004, San Francisco, CA 94143, USA. locksley@medicine.ucsf.edu.
Jennifer K
JK
Bando
Jesse C
JC
Nussbaum
Hong-Erh
HE
Liang
Richard M
RM
Locksley
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D008214:Lymphocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus; D011014:Pneumonia / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000502:physiology; D017206:Strongylida Infections / Q000276:immunology
D016207:Cytokines; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase
Arg1-YFP; ILC2; Nippostrongylus brasiliensis; Yarg; alternatively activated macrophages