Jak3 is involved in dendritic cell maturation and CCR7-dependent migration.
BACKGROUND
CCR7-mediated signalling is important for dendritic cell maturation and homing to the lymph nodes. We have previously demonstrated that Jak3 participates in the signalling pathway of CCR7 in T lymphocytes.


RESULTS
Here, we used Jak3(-/-) mice to analyze the role of Jak3 in CCR7-mediated dendritic cells migration and function. First, we found no differences in the generation of DCs from Jak3(-/-) bone marrow progenitors, when compared to wild type cells. However, phenotypic analysis of the bone marrow derived DCs obtained from Jak3(-/-) mice showed reduced expression of co-stimulatory molecules compared to wild type (Jak3(+/+)). In addition, when we analyzed the migration of Jak3(-/-) and Jak3(+/+) mature DCs in response to CCL19 and CCL21 chemokines, we found that the absence of Jak3 results in impaired chemotactic responses both in vitro and in vivo. Moreover, lymphocyte proliferation and contact hypersensitivity experiments showed that DC-mediated T lymphocyte activation is reduced in the absence of Jak3.


CONCLUSIONS
Altogether, our data provide strong evidence that Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway.
Rivas-Caicedo
Ana
A
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, México, DF, Mexico.
Soldevila
Gloria
G
Fortoul
Teresa I
TI
Castell-Rodríguez
Andrés
A
Flores-Romo
Leopoldo
L
García-Zepeda
Eduardo A
EA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D053616:Janus Kinase 3 / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D054400:Receptors, CCR7 / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3