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The complex role of IL-36 γ during intestinal inflammation

The complex role of IL-36 γ during intestinal inflammation. Oscar Medina. DISCLOSURES. Nothing to disclose. Intestinal Immune System. Annu . Rev. Immunol . 27 : 313. Healthy and Inflamed Intestine LP M Φ. Healthy Intestine. Inflamed Intestine. Ly6C. CX 3 CR1. CCR2.

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The complex role of IL-36 γ during intestinal inflammation

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  1. The complex role of IL-36γ during intestinal inflammation Oscar Medina

  2. DISCLOSURES • Nothing to disclose

  3. Intestinal Immune System Annu. Rev. Immunol. 27:313

  4. Healthy and Inflamed Intestine LP MΦ Healthy Intestine Inflamed Intestine Ly6C CX3CR1 CCR2 CD45+IAb+ CD11b+F4/80+ CD45+IAb+ CD11b+F4/80+ IL-10 TNFα Retinoic acid Resident Mφ Infiltrating Mφ Immunity14:1076 Mucosal Immunol.6:498

  5. IL-36γis expressed by Ly6C+ inflammatory LP Mø

  6. IL-36γis expressed during experimental colitis and human IBD * * * * * * ND * *

  7. IL-36γinduces IL-23 and IL-23R in vivo * *

  8. IL-36γ promotes Th17/22 and inhibits Foxp3+ T cells *

  9. Loss of IL-36R ameliorates DSS colitis * * * Il1rl2+/+ * * * * * Il1rl2-/-

  10. IL-36R signaling induces IL-22 * * * * * * * * * * *

  11. IL-36 promotes mucosal healing/repair via the AhR/IL-22 axis * * ND ND * * * * Il1rl2+/+ Il1rl2+/+FICZ Il1rl2-/- Il1rl2-/- FICZ

  12. Summary Injury Phase Resolution Phase S100A Reg3β IL-22 Nφ ROS Nφ RORγt Th22 DC ILC RORγt Mφ ? ? IL-36γ Induced by bacterial componentsPromotes Th1/17 responsesInhibits iTregdifferentiation IL-36γ Activates AhR Induces IL-22 Th17 Th1 Treg Promotes healing/repair Exacerbates DSS colitis

  13. Acknowledgements Tim Denning Duke Geem Charles Parkos AsmaNusrat Ifor Williams Aaron Rae Jennifer Towne Funding:

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