Loss of IL-1R1 and IL-23R signaling in type 3 innate lymphoid cells (ILC3) lose their identity and can transdifferentiate into ILC1s and ILC2s

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B718
Abstract ID: 5997

Presenting Author:
Teruyuki Sano , Assistant Professor at Univ. of Illinois, Chicago

Abstract:

Innate lymphoid cells (ILCs) play a pivotal role in maintaining tissue homeostasis. Type 1, 2, and 3 ILCs have emerged as tissue-resident innate counterparts of T helper 1 (Th1), Th2, and Th17 cells owing to their similar transcription factor and cytokine expression profiles. Unlike T cells, ILCs can be rapidly activated by cytokine signaling without education by antigen presentation. Conversely, under ILC-intensive conditions, ILCs cannot expand as effectively as T cells. Plasticity between ILC1 and ILC3 has been reported and contributes to maintaining ILC1/ILC3 balance in their demanding condition. We found that ILC3s in the colon can be activated during Type 3 inflammation, with corresponding reductions and increases in ILC2 and ILC3 numbers, respectively. In contrast, during Type 2-mediated colitis, ILC2s are highly activated and expand. However, plasticity between ILC2 and ILC3 are not reported yet. Fate mapping in ILC3-specific Cre recombinase Knock-in mice, newly generated in our lab, revealed that ILC3s can undergo conversion into not only ILC1s but also ILC2s. ILC3-specific IL-1R1 and IL-23R deficient mice showed less IL-22 producing ILC3s and decreased fate mapping positive ILC3s, and the numbers of fate mapping positive ILC1s and ILC2s increased in their gut. These suggested that the identity of ILC3s can be synergistically maintained by commensal-derived IL-1R1 and IL-23R signaling, and if the identity is lost, ILC3s can be converted into ILC1s and ILC2s.