Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation.

Abstract

BACKGROUND:

Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear.

OBJECT:

We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist.

METHODS:

We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice.

RESULTS:

The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages.

CONCLUSION:

These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.

• Authors: Mayo Kondo, Toshifumi Tezuka, Hirohisa Ogawa, Kazuya Koyama, Hiroki Bando, Masahiko Azuma, Yasuhiko Nishioka
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 182 Issue 1 Pg. 1-13 ( 2021) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 32846422 (Publication Type: Journal Article)
• Copyright: © 2020 S. Karger AG, Basel.

Chemical References

• Allergens
• Cytokines
• Lysophospholipids
• Receptors, Lysophosphatidic Acid
• lysophosphatidic acid

Topics

• Allergens (immunology)
• Animals
• Asthma (immunology)
• Bronchial Hyperreactivity (diagnosis, immunology)
• Cell Differentiation (drug effects)
• Cytokines (biosynthesis)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Lysophospholipids (pharmacology)
• Macrophages (immunology, metabolism)
• Mice
• Plethysmography
• Pyroglyphidae (immunology)
• Receptors, Lysophosphatidic Acid (antagonists & inhibitors, metabolism)
• Th2 Cells (drug effects, immunology, metabolism)