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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

MyD88 Signaling Pathway Is Involved in Renal Fibrosis by Favoring a T(H)2 Immune Response and Activating Alternative M2 Macrophages

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Braga, Tarcio Teodoro [1] ; Correa-Costa, Matheus [1] ; Souza Guise, Yuri Felipe [1] ; Castoldi, Angela [2] ; de Oliveira, Cassiano Donizetti [2] ; Hyane, Meire Ioshie [1] ; Cenedeze, Marcos Antonio [2] ; Teixeira, Simone Aparecida [3] ; Muscara, Marcelo Nicolas [3] ; Perez, Katia Regina [4] ; Cuccovia, Iolanda Midea [4] ; Pacheco-Silva, Alvaro [2] ; Goncalves, Giselle Martins [1] ; Saraiva Camara, Niels Olsen [1, 2]
Total Authors: 14
[1] Univ Sao Paulo, Lab Transplantat Immunobiol, Dept Immunol, Inst Biomed Sci 4, BR-05508900 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Lab Clin & Expt Immunol, Div Nephrol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
[4] Univ Sao Paulo, Dept Biochem, Inst Chem, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Molecular Medicine; v. 18, n. 8, p. 1231-1239, AUG 2012.
Web of Science Citations: 55

Inflammation contributes to the pathogenesis of chronic kidney disease (CKD). Molecules released by the inflamed injured tissue can activate toll-like receptors (TLRs), thereby modulating macrophage and CD4(+) T-cell activity. We propose that in renal fibrogenesis. M2 macrophages are recruited and activated in a T helper subset 2 cell (T(H)2)-prone inflammatory milieu in a MyD88-dependent manner. Mice submitted to unilateral ureteral ligation (UUO) demonstrated an increase in macrophage infiltration with collagen deposition after 7 d. Conversely, TLR2, TLR4 and MyD88 knockout (KO) mice had an improved renal function together with diminished TH2 cytokine production and decreased fibrosis formation. Moreover, TLR2, TLR4 and MyD88 KO animals exhibited less M2 macrophage infiltration, namely interleukin (IL)-10(+) and CD206(+). CD11b(high) cells, at 7 d after surgery. We evaluated the role of a T(H)2 cytokine in this context, and observed that the absence of IL-4 was associated with better renal function, decreased IL-13 and TGF-beta levels, reduced arginase activity and a decrease in fibrosis formation when compared with IL-12 KO and wild-type (WT) animals. Indeed, the better renal outcomes and the decreased fibrosis formation were restricted to the deficiency of IL-4 in the hematopoietic compartment. Finally, macrophage depletion, rather than the absence of T cells, led to reduced lesions of the glomerular filtration barrier and decreased collagen deposition. These results provide evidence that future therapeutic strategies against renal fibrosis should be accompanied by the modulation of the M1 :M2 and T(H)1:T(H)2 balance, as T(H)2 and M2 cells are predictive of fibrosis toward mechanisms that are sensed by innate immune response and triggered in a MyD88-dependent pathway. Online address: doi: 10.2119/molmed.2012.00131 (AU)

FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants