CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells

Tissue-resident CD8+T cells drive age-associated chronic lung sequelae following viral pneumonia

“…The heightened expression of these molecules confers CD8 + T RM cells with superb antiviral function, but may potentially cause bystander tissue inflammation and injury [41]. In experimental models, both CD4 + and CD8 + T RM cells have been implicated in causing tissue immunopathology ranging from persistent allergic inflammation to inflammatory bowel disease [61, 62]. Previous reports have demonstrated that influenza infection in young mice leads to chronic inflammation and collagen deposition [24].…”

Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

“…Notably, metalloproteases, ECM components, and specific integrins have also been shown to be enriched in CD8 + and Th1 Trm cells in other experimental systems, suggesting that regulation and interaction with the ECM may play an important role in the development, maintenance, and function of Trm cells in various tissues (Mackay et al, 2013;Wakim et al, 2012;Pan et al, 2017;Beura et al, 2019). Lastly, a recent study using Aspergillus fumigatus fungal extract to promote airway inflammation in mice found that effector CD4 + T cells expressing CD69 are enriched for genes involved in ECM biology and fibrosis, indicating that effector CD4 + T cells are also capable of directly regulating the ECM within the lung during active inflammation (Ichikawa et al, 2019).…”

“…Previous studies investigating the function of Th2 Trm cells have relied on strategies to decrease the numbers of circulating T cells, including treatment with the S1P1 agonist FTY720 or anti-Thy1 antibody (Hondowicz et al, 2016;Turner et al, 2018;Ichikawa et al, 2019). Notably, decreasing circulating T cells during allergen rechallenge did not significantly reduce the number of allergen-specific CD4 + T cells within the lung or the allergen recall response, suggesting circulating memory Th2 cells do not play a significant role (Hondowicz et al, 2016;Turner et al, 2018;Ichikawa et al, 2019). While FTY720 efficiently sequesters naive T cells in LNs, it is less efficient at causing lymphopenia of memory T cells (Hofmann et al, 2006).…”

Divergence of Tissue-Memory T Cells: Distribution and Function-Based Classification

“…Although the actual role of CD103 in their localization within the stroma is largely unknown, canonical Trm cell transcriptional signatures and superior polyfunctionality (Th1 cytokines) has been reported for CD103 + CD4 + Trm cells (Watanabe et al 2015;Oja et al 2018). In contrast, in a mouse model of chronic antigen exposure, antigen-specific CD103 − CD4 + Trm cells generated in the lung display a greater ability to secrete proinflammatory cytokines than their CD103 + counterparts, and cause fibrotic responses through elevated production of Th2 cytokines, including IL-4, IL-5, and IL-13 (Ichikawa et al 2019). IL-33 signaling accelerates the generation of the pathogenic subpopulation of resident CD103 − CD4 + T cells, while TGF-β potentially promotes the establishment of CD103 + FoxP3 + CD4 + T cells with regulatory capacities (Morimoto et al 2018;Ichikawa et al 2019).…”