PMID- 15147562
OWN - NLM
STAT- MEDLINE
DCOM- 20040625
LR  - 20181113
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 112
IP  - 2
DP  - 2004 Jun
TI  - Impaired chemokine-induced migration during T-cell development in the absence of 
      Jak 3.
PG  - 191-200
AB  - The arrival of bone marrow T-cell progenitors to the thymus, and the directed 
      migration of thymocytes, are thought to be regulated by the expression of 
      chemokines and their receptors. Recent data has shown that the Jak/Stat 
      signalling pathway is involved in chemokine receptor signalling. We have 
      investigated the role of Jak 3 in chemokine-mediated signalling in the thymus 
      using Jak 3(-/-) mice. These mice show defects in T-cell development, as well as 
      in peripheral T-cell function, resulting in a hypoplastic thymus and an altered 
      T-cell homeostasis. Here we demonstrate, for the first time, that bone marrow 
      progenitors and thymocytes from Jak 3(-/-) mice have decreased chemotactic 
      responses to CXCL12 and CCL25. We also show that Jak 3 is involved in signalling 
      through CCR9 and CXCR4, and that specific inhibition of Jak 3 in wild-type 
      progenitors and thymocytes decreases their chemotactic responses towards CCL25 
      and CXCL12. Finally, quantitative reverse transcription-polymerase chain reaction 
      analysis showed that thymocytes from Jak 3(-/-) mice express similar levels of 
      CXCR4 and CCR9 compared to wild-type mice. Altogether, deficient CCL25- and 
      CXCL12-induced migration could result in a homing defect of T-cell progenitors to 
      the thymus, as well as in a deficient thymocyte migration through the thymic 
      stroma. Our results strongly suggest that the absence of Jak 3 affects T-cell 
      development, not only through an impaired interleukin-7 receptor (IL-7R)-mediated 
      signalling, but also through impaired chemokine-mediated responses, which are 
      crucial for thymocyte migration and differentiation.
FAU - Soldevila, Gloria
AU  - Soldevila G
AD  - Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad 
      Nacional Autonoma de Mexico, Mexico. soldevi@servidor.unam.mx
FAU - Licona, Ileana
AU  - Licona I
FAU - Salgado, Alfonso
AU  - Salgado A
FAU - Ramirez, Marcela
AU  - Ramirez M
FAU - Chavez, Ramses
AU  - Chavez R
FAU - Garcia-Zepeda, Eduardo
AU  - Garcia-Zepeda E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (CC chemokine receptor 9)
RN  - 0 (Ccl25 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CC)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Quinazolines)
RN  - 0 (Receptors, CCR)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (WHI P131)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak3 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Animals
MH  - Chemokine CXCL12
MH  - Chemokines/*immunology
MH  - Chemokines, CC/immunology
MH  - Chemokines, CXC/immunology
MH  - Chemotaxis, Leukocyte/drug effects/*immunology
MH  - Dose-Response Relationship, Immunologic
MH  - Hematopoietic Stem Cells/immunology
MH  - Janus Kinase 3
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/*immunology
MH  - Quinazolines/pharmacology
MH  - Receptors, CCR
MH  - Receptors, CXCR4/metabolism
MH  - Receptors, Chemokine/metabolism
MH  - T-Lymphocytes/*immunology
MH  - Thymus Gland/immunology
MH  - Tyrosine/metabolism
PMC - PMC1782482
EDAT- 2004/05/19 05:00
MHDA- 2004/06/26 05:00
PMCR- 2005/06/01
CRDT- 2004/05/19 05:00
PHST- 2004/05/19 05:00 [pubmed]
PHST- 2004/06/26 05:00 [medline]
PHST- 2004/05/19 05:00 [entrez]
PHST- 2005/06/01 00:00 [pmc-release]
AID - IMM1863 [pii]
AID - 10.1111/j.1365-2567.2004.01863.x [doi]
PST - ppublish
SO  - Immunology. 2004 Jun;112(2):191-200. doi: 10.1111/j.1365-2567.2004.01863.x.