Progenitor T cells drive chronic pulmonary type 2 inflammation

Area of Science:

• Immunology
• Cell Biology
• Respiratory Medicine

Background:

• Type 2 inflammation is characterized by persistent CD4+ Th2 cell responses, unlike adaptive immunity collapse in chronic infections.
• The cellular mechanisms sustaining chronic type 2 inflammation and preventing T cell exhaustion are not well understood.
• Acute type 2 inflammation involves short-lived Th2 effector cells and type 2 innate lymphocytes (ILC2s).

Purpose of the Study:

• To define the cellular landscape of Th2 cells in chronic type 2 inflammation.
• To investigate the mechanisms maintaining sustained Th2 responses in the lung.
• To identify novel cell populations involved in chronic allergic inflammation.

Main Methods:

• Established a mouse model of long-term pulmonary allergen exposure.
• Analyzed Th2 cell populations in lung parenchyma during chronic inflammation using transcriptomics.
• Compared type 2 inflammation transcriptomes with chronic viral infection data.

Main Results:

• Chronic type 2 inflammation was sustained for at least 4 months in mice.
• Identified an expanded T cell factor-1 (TCF1)-expressing progenitor-like Th2 population in the lung.
• These lung Th2 progenitors exhibited self-renewal and effector differentiation, sustaining inflammation without persistent antigen.

Conclusions:

• Tissue Th2 progenitors are a distinct cellular state crucial for maintaining chronic type 2 inflammation.
• These progenitors are sufficient to initiate and sustain type 2 inflammation, independent of lymph node support.
• Lung Th2 progenitor maintenance involves B cells and is associated with lymphoid tissue formation.