The formation and function of tertiary lymphoid follicles in chronic pulmonary inflammation

Abstract

SummaryTertiary lymphoid follicles (TLFs) can develop in the respiratory tract in response to infections or chronic inflammation. However, their functional relevance remains unclear because they are implicated in both protective and pathological responses. In contrast to homeostatic conditions, external antigens and damage to the lung tissue may drive TLF formation in inflamed lungs, and once established, the presence of pulmonary TLFs may signal the progression of chronic lung disease. This novel concept will be discussed in light of recent work in chronic obstructive pulmonary disease and how changes in the pulmonary microbiota may drive and direct TLF formation and function. We will also discuss the cellularity of TLFs at the pulmonary mucosa, with emphasis on the potential roles of lymphoid tissue inducer cells, and B-and T-cell aggregates, and will examine the function of key chemokines and cytokines including CXCL13 and interleukin-17, in the formation and maintenance of pulmonary TLFs.

Tissue-resident CD4+T helper cells assist protective respiratory mucosal B and CD8+T cell memory responses

“…The roles of iBALT and T RH in the development of chronic lung conditions following influenza infection needs further investigations. Additionally, tertiary lymphoid (B/T) aggregates or iBALT-like structures have been observed in many chronic lung diseases including asthma, pulmonary fibrosis, COPD (Chronic obstructive pulmonary disease) etc 77, 78, 79, 80 . It was speculated that these tertiary lymphoid structures may play important roles in modulating the disease progression in those chronic lung conditions 47, 79 .…”

Rituximab Monotherapy for Common Variable Immune Deficiency-Associated Granulomatous-Lymphocytic Interstitial Lung Disease

“…TLSs develop postnatally in response to environmental antigenic stimulation, and are organized structures, similar to secondary lymphoid organs such as lymph nodes and the spleen. 6 TLSs have been found in many chronic pulmonary diseases, including mycobacterial infection, COPD, 7 hypersensitivity pneumonitis, asthma, and pulmonary complications from autoimmune diseases such as rheumatoid arthritis 8 and Sjögren's syndrome. Furthermore, not only are TLSs more prevalent in autoimmune-associated interstitial lung disease compared with normal and noninflammatory lung conditions, but the presence of TLSs has also been associated with increased alveolar anti-cyclic citrullinated peptide antibodies and local tissue damage in this context, suggesting that TLSs are not only bystanders in chronic inflammation but may play a role in pathogenesis in the context of autoimmune disease.…”

Perivascular adipose tissue inflammation in vascular disease

“…TLOs are organized aggregates of immune cells formed in post‐embryonic life (GeurtsvanKessel et al , ). They can be found around blood vessels in chronic allograft rejection, atherosclerosis and pulmonary hypertension and in patients with chronic obstructive pulmonary disease (Neyt et al , ; Perros et al , ; Yadava et al , ). Interestingly, TLO formation is reversible when inflammation is resolved or after therapeutic intervention (Drayton et al , ).…”