MHC class II-associated invariant chain isoforms regulate pulmonary immune responses

Area of Science:

• Immunology
• Allergy and Asthma Research
• Molecular Biology

Background:

• Asthma is a chronic lung inflammatory disease with reversible airway obstruction and hyperresponsiveness.
• Immune responses in asthma involve MHC class II-restricted antigen presentation, CD4(+) T cell stimulation, and Th2 cytokine production.
• Conventional MHC class II pathways require invariant chain (Ii) and HLA-DM, but alternative antigen presentation routes may exist.

Purpose of the Study:

• To investigate the roles of invariant chain (Ii) and HLA-DM in a mouse model of allergic lung inflammation.
• To determine the distinct contributions of p31 Ii and p41 Ii isoforms to the development of asthma-like responses.

Main Methods:

• Utilized genetically modified mice lacking Ii or H2-M (the mouse homolog of HLA-DM).
• Compared allergen-induced lung inflammation, eosinophilia, IgE production, and airway hyperresponsiveness (AHR) in mice expressing only p31 Ii or p41 Ii.
• Employed a mouse model of allergic inflammation involving sensitization and challenge with ovalbumin (OVA).

Main Results:

• Mice lacking Ii or H2-M failed to develop lung inflammation or AHR after OVA challenge.
• Expression of either p31 Ii or p41 Ii alone supported allergen-induced lung inflammation and eosinophilia.
• Mice expressing only p31 Ii showed reduced IgE production and AHR compared to p41 Ii mice.

Conclusions:

• Ii and H2-M are essential for controlling immune responses in the lung during allergic inflammation.
• The p31 Ii and p41 Ii isoforms have nonredundant functions in the development of lung immunity.
• Complete immune responses in the lung necessitate the expression of the p41 Ii isoform.