Complement factor C5 inhibition reduces type 2 responses without affecting group 2 innate lymphoid cells in a house dust mite induced murine asthma model.

Abstract

BACKGROUND:

Complement factor C5 can either aggravate or attenuate the T-helper type 2 (TH2) immune response and airway hyperresponsiveness (AHR) in murine models of allergic asthma. The effect of C5 during the effector phase of allergen-induced asthma is ill-defined.

OBJECTIVES:

We aimed to determine the effect of C5 blockade during the effector phase on the pulmonary TH2 response and AHR in a house dust mite (HDM) driven murine asthma model.

METHODS:

BALB/c mice were sensitized and challenged repeatedly with HDM via the airways to induce allergic lung inflammation. Sensitized mice received twice weekly injections with a blocking anti-C5 or control antibody 24 h before the first challenge.

RESULTS:

HDM challenge in sensitized mice resulted in elevated C5a levels in bronchoalveolar lavage fluid. Anti-C5 administered to sensitized mice prior to the first HDM challenge prevented this rise in C5a, but did not influence the influx of eosinophils or neutrophils. While anti-C5 did not impact the recruitment of CD4 T cells upon HDM challenge, it reduced the proportion of TH2 cells recruited to the airways, attenuated IL-4 release by regional lymph nodes restimulated with HDM ex vivo and mitigated the plasma IgE response. Anti-C5 did not affect innate lymphoid cell (ILC) proliferation or group 2 ILC (ILC2) differentiation. Anti-C5 attenuated HDM induced AHR in the absence of an effect on lung histopathology, mucus production or vascular leak.

CONCLUSIONS:

Generation of C5a during the effector phase of HDM induced allergic lung inflammation contributes to TH2 cell differentiation and AHR without impacting ILC2 cells.

• Authors: Jack Yang, Ivan Ramirez Moral, Cornelis van 't Veer, Alex F de Vos, Regina de Beer, Joris J T H Roelofs, B Paul Morgan, Tom van der Poll
• Journal: Respiratory research (Respir Res) Vol. 20 Issue 1 Pg. 165 (Jul 24 2019) ISSN: 1465-993X [Electronic] England
• PMID: 31340811 (Publication Type: Journal Article)

Chemical References

• Methacholine Chloride
• Complement C5a

Topics

• Animals
• Asthma (chemically induced, immunology, prevention & control)
• Complement C5a (antagonists & inhibitors, immunology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Immunity, Innate (drug effects, immunology)
• Lymphocytes (drug effects, immunology)
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Inbred BALB C
• Pyroglyphidae (immunology)
• Th2 Cells (drug effects, immunology)