Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation.

Abstract

Natural helper (NH) cells are innate lymphoid cells (ILCs) that produce T helper-2 (Th2)-cell-type cytokines in the lung- and gut-associated lymphoid tissues. Currently, the lineage relationship between NH cells in different tissues and between NH cells and interleukin-22 (IL-22)-producing retinoic-acid-receptor-related orphan receptor (ROR)γt-positive ILCs is unclear. Here, we report that NH cells express RORα, but not RORγt. RORα-deficient, but not RORγt-deficient, mice lacked NH cells in all tissues, whereas all other lymphocytes, including RORγt(+) ILCs, were unaffected. NH-cell-deficient mice generated by RORα-deficient bone-marrow transplantation had normal Th2 cell responses but failed to develop acute lung inflammation in response to protease allergen, thus confirming the essential role of NH cells in allergic lung inflammation. We have also identified RORα-dependent NH cell progenitors in the bone marrow. Thus, all NH cells belong to a unique RORα-dependent cell lineage separate from other lymphoid cell lineages.

• Authors: Timotheus Y F Halim, Aric MacLaren, Mark T Romanish, Matthew J Gold, Kelly M McNagny, Fumio Takei
• Journal: Immunity (Immunity) Vol. 37 Issue 3 Pg. 463-74 (Sep 21 2012) ISSN: 1097-4180 [Electronic] United States
• PMID: 22981535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Antigens, Ly
• Il2rg protein, mouse
• Interleukin Receptor Common gamma Subunit
• Ly6a protein, mouse
• Membrane Proteins
• Nuclear Receptor Subfamily 1, Group F, Member 1
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Rora protein, mouse
• Proto-Oncogene Proteins c-kit
• Papain

Topics

• Allergens (immunology)
• Animals
• Antigens, Ly (genetics, immunology)
• Bone Marrow Cells (immunology, metabolism)
• Bone Marrow Transplantation
• Cell Lineage (immunology)
• Cells, Cultured
• Female
• Flow Cytometry
• Interleukin Receptor Common gamma Subunit (genetics, immunology)
• Lymphocytes (immunology, metabolism)
• Male
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, Knockout
• Mice, SCID
• Nuclear Receptor Subfamily 1, Group F, Member 1 (genetics, immunology)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, immunology)
• Papain (immunology)
• Pneumonia (genetics, immunology)
• Proto-Oncogene Proteins c-kit (genetics, immunology)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• Th2 Cells (immunology, metabolism)