Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.616309
Keywords
CD4+resident memory T cells; Aspergillus fumigatus; lung fibrosis; ATAC-seq; inducible bronchus-associated lymphoid tissue (iBALT); pathogenic T cell
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) [JP19H05650, 20H03685, 17K08876, 18K07164, 19K16683]
- Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, AMED [JP20ek0410082, JP20ek0410060, JP19ek0410045]
- AMED - PRIME, AMED [JP20gm6110005]
- AMED-CREST, AMED [JP20gm1210003]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- MSD Life Science Foundation
- Naito Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [19K16683, 20H03685, 17K08876, 18K07164] Funding Source: KAKEN
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Memory T cells play a crucial role in protecting the body against pathogens over a long period of time. T-RM cells, a subset of memory T cells, provide frontline defense at mucosal tissue sites. CD4(+) T-RM cells have conflicting roles in protective and pathogenic immune responses.
Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time. Three major subsets of memory T cells; effector memory T (T-EM) cells, central memory T (T-CM) cells, and tissue-resident memory T (T-RM) cells have been identified. The most recently identified subset, T-RM cells, is characterized by the expression of the C-type lectin CD69 and/or the integrin CD103. T-RM cells persist locally at sites of mucosal tissue, such as the lung, where they provide frontline defense against various pathogens. Importantly, however, T-RM cells are also involved in shaping the pathology of inflammatory diseases. A number of pioneering studies revealed important roles of CD8(+) T-RM cells, particularly those in the local control of viral infection. However, the protective function and pathogenic role of CD4(+) T-RM cells that reside within the mucosal tissue remain largely unknown. In this review, we discuss the ambivalent feature of CD4(+) T-RM cells in the protective and pathological immune responses. We also review the transcriptional and epigenetic characteristics of CD4(+) T-RM cells in the lung that have been elucidated by recent technical approaches. A better understanding of the function of CD4(+) T-RM cells is crucial for the development of both effective vaccination against pathogens and new therapeutic strategies for intractable inflammatory diseases, such as inflammatory bowel diseases and chronic allergic diseases.
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