{"doi":"10.18632/oncotarget.27509","title":"CrkL is required for donor T cell migration to GvHD target organs","abstract":"// Nathan H. Roy 1 , Mahinbanu Mammadli 2 , Janis K. Burkhardt 1 and Mobin Karimi 2 1 Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 2 Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA Correspondence to: Mobin Karimi, email: karimim@upstate.edu Keywords: graft-versus-host disease; CrkL; T cell; migration; inflammation Received: January 03, 2020     Accepted: February 17, 2020     Published: April 28, 2020 ABSTRACT The success of cancer therapies based on allogeneic hematopoietic stem cell transplant relies on the ability to separate graft-versus-host disease (GvHD) from graft-versus-tumor (GVT) responses. Controlling donor T cell migration into peripheral tissues is a viable option to limit unwanted tissue damage, but a lack of specific targets limits progress on this front. Here, we show that the adaptor protein CrkL, but not the closely related family members CrkI or CrkII, is a crucial regulator of T cell migration. In vitro , CrkL-deficient T cells fail to polymerize actin in response to the integrin ligand ICAM-1, resulting in defective migration. Using a mouse model of GvHD/GVT, we found that while CrkL-deficient T cells can efficiently eliminate hematopoietic tumors they are unable to migrate into inflamed organs, such as the liver and small intestine, and thus do not cause GvHD. These results suggest a specific role for CrkL in trafficking to peripheral organs but not the lymphatic system. In line with this, we found that although CrkL-deficient T cells could clear hematopoietic tumors, they failed to clear the same tumor growing subcutaneously, highlighting the role of CrkL in controlling T cell migration into peripheral tissues. Our results define a unique role for CrkL in controlling T cell migration, and suggest that CrkL function could be therapeutically targeted to enhance the efficacy of immunotherapies involving allogeneic donor cells.","journal":"Oncotarget","year":2020,"id":107240,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":491152,"name":"Mahinbanu Mammadli","orcid":null,"position":1,"is_corresponding":false},{"id":279477,"name":"Janis K. Burkhardt","orcid":"0000-0002-8176-1375","position":2,"is_corresponding":false},{"id":490105,"name":"Mobin Karimi","orcid":"0000-0002-3240-4814","position":3,"is_corresponding":false},{"id":313558,"name":"Nathan H. Roy","orcid":"0000-0003-1229-2808","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:12:34.898963Z","pmid":"32391120","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}