User:Michaelap25/sandbox

= Tissue-Resident memory T cells = Tissue-Resident memory T cells or TRM cells represent a lineage of T cells that occupies tissues (skin, lung, gastrointestinal tract, etc.) without recirculating. TRM cells are transcriptionally, phenotypically and functionaly distinct from central memory and effector memory T cells which recirculate between blood, the T cell zones of secondary lymphoid organs, lymph and nonlymphoid tissues. The role of TRM cells is provide superior protection against infection in extralymphoid tissues.

Phenotype
Main cell surface markers that has been associated with TRM in human tissues are CD69 and CD103. CD103 marker is expressed only by CD8+ TRM cells and not by CD4+ TRM cells. CD69 marker has key role in distinguishing T cells in tissues from those in circulation. However, expression levels can differ between T cells in different tissues. Another marker that can be used to separate  two TRM cell subsets  with distinct functions is CD49a. CD8+ CD49a+ TRM cells produce perforin and IFN-gamma, which is a key cytokine in clearing virus infections. CD8+ CD49a- TRM cells produce IL-17.

Development
TRM cells develop from circulating effector memory T cell precursors in response to antigen. The main role in formation of TRM cells has CD103 and expression of this integrin is dependent on the cytokine TGFβ. CD8+ effector T cells that lack TGFβ fail to upregulate CD103, and subsequently do not differentiate into TRM cells. The important role in development of TRM cells have various cytokines that support TRM cell formation and survival. For example homeostatic cytokine IL-15, pro-inﬂammatory cytokines such as IL-12 and IL-18, and barrier cytokines such as IL-33.

Function
TRM cells reside in many tissues that create barriers against outside environment and thus provide defense against incoming pathogens. In the skin, lung, brain, and vagina TRM cells are required to provide rapid control of infection and are more efficient that effector memory T cells. TRM cells also express granzyme B which help limit the spread of pathogens at the site of infection. TRM cells are able to activate innate and adaptive leukocytes to protect the host. .

Role in disease pathogenesis
Autoreactive TRM cells may induce some autoimmune disorders, such as multiple sclerosis, lupus nephritis, rheumatoid arthritis, autoimmune hepatis or psorasis.