PMID- 29296975 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2473-9529 (Print) IS - 2473-9537 (Electronic) IS - 2473-9529 (Linking) VI - 1 IP - 9 DP - 2017 Mar 28 TI - Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses. PG - 557-568 LID - 10.1182/bloodadvances.2016002360 [doi] AB - Dendritic cells (DCs) represent essential antigen-presenting cells that are critical for linking innate and adaptive immunity, and influencing T-cell responses. Among pattern recognition receptors, DCs express C-type lectin receptors triggered by both exogenous and endogenous ligands, therefore dictating pathogen response, and also shaping T-cell immunity. We previously described in rat, the expression of the orphan C-type lectin-like receptor-1 (CLEC-1) by DCs and demonstrated in vitro its inhibitory role in downstream T helper 17 (Th17) activation. In this study, we examined the expression and functionality of CLEC-1 in human DCs, and show a cell-surface expression on the CD16(-) subpopulation of blood DCs and on monocyte-derived DCs (moDCs). CLEC-1 expression on moDCs is downregulated by inflammatory stimuli and enhanced by transforming growth factor beta. Moreover, we demonstrate that CLEC-1 is a functional receptor on human moDCs and that although not modulating the spleen tyrosine kinase-dependent canonical nuclear factor-kappaB pathway, represses subsequent Th17 responses. Interestingly, a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and is associated with a higher level of interleukin 17A (IL17A). Importantly, using CLEC-1-deficient rats, we showed that disruption of CLEC-1 signaling led to an enhanced Il12p40 subunit expression in DCs, and to an exacerbation of downstream in vitro and in vivo CD4(+) Th1 and Th17 responses. Collectively, our results establish a role for CLEC-1 as an inhibitory receptor in DCs able to dampen activation and downstream effector Th responses. As a cell-surface receptor, CLEC-1 may represent a useful therapeutic target for modulating T-cell immune responses in a clinical setting. FAU - Lopez Robles, Maria Dolores AU - Lopez Robles MD AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Pallier, Annaick AU - Pallier A AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Huchet, Virginie AU - Huchet V AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Le Texier, Laetitia AU - Le Texier L AD - Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. FAU - Remy, Severine AU - Remy S AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Braudeau, Cecile AU - Braudeau C AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; and. FAU - Delbos, Laurence AU - Delbos L AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Moreau, Aurelie AU - Moreau A AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Louvet, Cedric AU - Louvet C AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Brosseau, Carole AU - Brosseau C AD - IHU Cesti, Nantes, France. AD - Institut du thorax UMR1087, INSERM, and. FAU - Royer, Pierre-Joseph AU - Royer PJ AD - IHU Cesti, Nantes, France. AD - Institut du thorax UMR1087, INSERM, and. FAU - Magnan, Antoine AU - Magnan A AD - IHU Cesti, Nantes, France. AD - Institut du thorax UMR1087, INSERM, and. FAU - Halary, Franck AU - Halary F AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Josien, Regis AU - Josien R AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; and. AD - Faculte de Medecine, Universite de Nantes, Nantes, France. FAU - Cuturi, Maria-Cristina AU - Cuturi MC AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Anegon, Ignacio AU - Anegon I AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. FAU - Chiffoleau, Elise AU - Chiffoleau E AUID- ORCID: 0000-0001-6167-682X AD - Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Universite de Nantes, Nantes, France. AD - Institut de Transplantation Urologie Nephrologie (ITUN), CHU Nantes, Nantes, France. AD - IHU Cesti, Nantes, France. AD - LabEx IGO Immunotherapy Graft, Oncology, Nantes, France. LA - eng PT - Journal Article DEP - 20170322 PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 PMC - PMC5728597 COIS- Conflict-of-interest disclosure: The authors declare no competing financial interests. EDAT- 2018/01/04 06:00 MHDA- 2018/01/04 06:01 PMCR- 2017/03/22 CRDT- 2018/01/04 06:00 PHST- 2016/10/20 00:00 [received] PHST- 2017/02/22 00:00 [accepted] PHST- 2018/01/04 06:00 [entrez] PHST- 2018/01/04 06:00 [pubmed] PHST- 2018/01/04 06:01 [medline] PHST- 2017/03/22 00:00 [pmc-release] AID - 2016/002360 [pii] AID - 10.1182/bloodadvances.2016002360 [doi] PST - epublish SO - Blood Adv. 2017 Mar 22;1(9):557-568. doi: 10.1182/bloodadvances.2016002360. eCollection 2017 Mar 28.