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Project #17567
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#17567 : Role of the histone demethylase Kdm6b in ILC2 maturation and functional activation
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Name of Applicant : Elsa Bourayou
Date of application : 28-09-2021
Unit : Group: Rachel Golub
Location : Metchnikoff, 5th floor, room 5006
Phone : 0651909844
@ Mail : elsa.bourayou@pasteur.fr
@ PI-Mail : rachel.golub@pasteur.fr

Project context and summary :

Kdm6b is a histone demethylase that specifically demethylates tri-methylated histone3 lysine27 (H3K27me3), a repressive mark responsible for gene silencing. Its removal by Kdm6b enables the transcription of specific target genes. Kdm6b is expressed in many cell types such as neurons, hematopoietic stem cells, leukocytes or fibroblasts. Type 2 Innate Lymphoid cells (ILC2) are the innate counterpart of Th2 lymphocytes enriched at the barrier surfaces where they play a role in tissue repair and anti-helminth defense. Previous work from our team showed that Kdm6b expression is upregulated in IL-33-activated ILC2s. Using a IL7RCre-Kdm6bflox mouse model that specifically deletes Kdm6b in all IL7R-expressing cells including ILC2, we observed decreased ILC2 numbers in bone marrow (BM) as well as in peripheral organs. qRT-PCR on sorted Kdm6b-deficient BM ILC2 precursors revealed decreased expression of several transcription factors as well as St2, the IL-33 receptor, all involved in ILC2 maturation and activation. Stimulation via intravenous (i.v) injections of IL-33 showed alteration of cytokine production in Kdm6b-deficient ILC2s compared to WT ILC2s, in BM as well as in the periphery. This observation was confirmed using an IL-33-dependent asthma model, the papain model, where Kdm6b-deficient lung ILC2s displayed decreased secretion of inflammatory cytokines. Altogether, our results suggest a role for Kdm6b in ILC2 maturation and Th2 pathway maintenance through the IL-33/ST2 axis.


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Project Manager : rachel.legendre@pasteur.fr
Status : Pending


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