Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine.
OBJECTIVE
Chemokines are small proteins that direct leukocyte trafficking under homeostatic and inflammatory conditions. We analyzed the differential expression of chemokines in distinct segments of the intestine and investigated the importance of chemokines for the distribution of leukocytes in the intestine during homeostatic and inflammatory conditions.


METHODS
We analyzed messenger RNA for all known chemokines in different segments of the gut by quantitative polymerase chain reaction. To study the effect of multiple-chemokine blockade in the gut, we generated transgenic mice that expressed the chemokine binding protein M3 in the intestine (V-M3 mice). We used flow cytometry to evaluate the changes in the numbers of leukocytes.


RESULTS
We observed distinct chemokine expression profiles in the 6 segments of the gut. Some chemokines were expressed throughout the intestine (CCL28, CCL6, CXCL16, and CX3CL1), whereas others were expressed preferentially in the small (CCL25 and CCL5) or large intestine (CCL19, CCL21, and CXCL5). Expression of the chemokine blocker M3 in intestinal epithelial cells resulted in reduced numbers of B and T cells in Peyer's patches, reduced numbers of intraepithelial CD8alphabeta(+)/TCRalphabeta(+) and CD8alphaalpha(+)/TCRalphabeta(+) T cells, and reduced numbers of lamina propria CD8(+) T cells. Strikingly, M3 expression markedly reduced the number of eosinophils and macrophages in the small and large intestines. Dextran sulfate sodium treatment of control mice led to marked changes in the expression of chemokines and in the number of myeloid cells in the colon. These cellular changes were significantly attenuated in the presence of M3.


CONCLUSIONS
Our study reveals a complex pattern of chemokine expression in the intestine and indicates that chemokines are critical for leukocyte accumulation in the intestine during homeostasis and inflammation.
Shang
Limin
L
Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
Thirunarayanan
Nanthakumar
N
Viejo-Borbolla
Abel
A
Martin
Andrea P
AP
Bogunovic
Milena
M
Marchesi
Federica
F
Unkeless
Jay C
JC
Ho
Yin
Y
Furtado
Glaucia C
GC
Alcami
Antonio
A
Merad
Miriam
M
Mayer
Lloyd
L
Lira
Sergio A
SA
D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D016131:Lymphocyte Subsets; D051379:Mice; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology; D019707:Receptors, Chemokine / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D018925:Chemokines; C118862:M3 protein, Murine gammaherpesvirus; D019707:Receptors, Chemokine; D014764:Viral Proteins